Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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cell division cycle 42(CDC42) cell division cycle 42(CDC42) Related Genes Homo sapiens
CHROMOSOME 1, 7,
CYTOBAND 1p36.1, 7p11.2,
ENSEMBL_GENE_ID ENSG00000070831,
GENERIF_SUMMARY Our findings indicate that different signaling cascades resulting in the activation of ..or Cdc42 can modulate the exocytotic process of neuroendocrine cells., Cdc42 is required for capillary lumen formation by vascular endothelial cells in three-dimensional extracellular matrices, Data show that TGF-beta-induced rearrangements of the actin filament system required the activity of the Rho GTPases Cdc42 and RhoA, because ectopic expression of dominant negative mutant Cdc42 and RhoA abrogated the response., signaling to the cytoskeleton involves IQGAP1 as a component, role for small GTPase CDC42Hs in the generation of skeletal muscle tumors., Structural basis for the selective activation of Rho GTPases by Dbl exchange factors, SopE binds to and locks the switch I and switch II regions of human Cdc42(1-178) in a conformation that promotes guanine nucleotide release., Cdc42 play essential role in regulating the formation of dendritic processes by dendritic cell, Effect of Mg(2+) on the kinetics of guanine nucleotide binding and hydrolysis, The ability of a Cdc42(D118N) mutant to survive under apoptotic conditions accounts for its superior transforming activity compared to other activated versions of Cdc42., Rac1 and Cdc42 are activated independent of RhoG, Cdc42 is involved in the mediation of intracellular lipid transport., Cdc42/Rac1-dependent activation of the p21-activated kinase (PAK) regulates human platelet lamellipodia spreading., Rac/Cdc42-dependent activation of MAPK/ERK is a critical event in the immediate phagocytic response of PMNs to microbial challenge., Data show that inhibition of endogenous RhoA, Rac1, and Cdc42 by their respective dominant negative mutants inhibits neurotensin-induced interleukin-8 protein production and promoter activity., VE-cadherin can serve as a scaffold involved in Cdc42 activation at the endothelial plasma membrane., TRE17 coprecipitated specifically with the active forms of Cdc42 and Rac1 in vivo. TRE17 is part of a novel effector complex for Cdc42 and Rac1, potentially contributing to their effects on actin remodeling., Upregulation during arachidonic acid mediated HeLa cell adhesion., Instead of inducing neurite formation, a constitutively active form of human Cdc42 stimulates the proliferation of rat PC12 cells in the presence of nerve growth factor., Cdc42 regulates the activitity of p21-activated protein kinase 5, Activated Cdc42 at the leading edge of a neutrophil in culture helps orient the cell's axis in a signaling complex with G beta gamma, PAK1, and PIXalpha., Activated CDC42 helps orient the neutrophil's axis in a signaling complex with Gbeta gamma, PAK1, and PIXalpha., Directional sensing requires GNB1-mediated PAK1 and PIX alpha-dependent activation of Cdc42., BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis., Activation of the small Rho GTPase Cdc42 plays a specific role in the actin reorganization mediated by CD28 in human T cells., direct activation of Cdc42 and Rac1 by invasive Salmonella is a prerequisite of Salmonella-mediated death of U937 cells., in neutrophils, Rac2 and Cdc42 are involved in FcR- and CR3-induced activation and for properly functioning signal transduction involved in the generation of oxygen radicals., The reorganization of actins into podosomes is controlled by CDC42 GTP-binding protein., Cdc42 signaling has a role in apoA-I-induced cholesterol efflux, The delayed activation of Cdc42 represents a negative-feedback mechanism that signals adherens junction reassembly after the increase in endothelial permeability induced by inflammatory mediators such as thrombin., Cdc42 synergistically with Rac1 induces lamellipodia and membrane ruffles in EGF-stimulated cells., Cdc42 signal transduction to the nucleus requires ACK-1 and ACK-2, Cdc42 has a role in mediation of UV-induced p38 activation by G protein betagamma subunits, novel role for Smad7 in TGF-beta-dependent activation of Cdc42, C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell actin remodeling at the attachment site., a specific region in Cdc42 confers the binding specificity to activated Cdc42-associated kinase, cross-talk between Rac and Cdc42 GTPases regulates generation of reactive oxygen species, role of frabin, a guanine nucleotide exchange factor specific for Cdc42, in the activation of Cdc42 during Cryptosporidium parvum infection of biliary epithelial cells, cdc42 has a role in activating c-Jun N-terminal kinase activation with Nck1, Both Cdc42 & Rac1 control the transport of essential immunostimulatory molecules to the DC surface. Cdc42 and Rac1 signaling controls DC morphology and conditions DCs for efficient CD8(+) T cell stimulation., Detailed analysis of backbone dynamics of the single-point mutant of Cdc42Hs(F28L) indicates how the mutation disrupts interactions that destabilize the local structure, leading to multiple time-scale motions of residues in the binding site., nucleotide-free Cdc42 might be sequestered by IQGAP1 to prevent signaling, localized activation in the trans-Golgi apparatus, microtubule-dependent Cdc42 activation at the cell periphery, and activation kinetics precisely coordinated with cell extension and retraction was revealed by a biosensor, Defined phospholipid oxidation products are capable of increasing EC barrier function via signaling mechanisms mediated by small GTPases Rac and Cdc42 leading to EC cytoskeletal remodeling and barrier restoration., actin has opposing roles in Cdc42p polarization, BNIP-2 in vivo induces cell dynamics by recruiting Cdc42, Distinct spatial association patterns between Cdc42 and its key effector proteins PAK1 and N-WASP controlling cytoskeletal remodeling were revealed., a Cdc42-MRCK signal mediates myosin-dependent cell motility and there is convergence between Rho and Cdc42 signalling, MMP-1 expression is maintained at a low level by Cdc42 via a repression of the Rac1 and ERK1/2 pathways when cell/extracellular-matrix interactions via integrins induce cytoskeleton organization, The cdc42 GTP-Binding Protein regulates the intracellular localization of PTEN in leukocytes and human transfected embryonic kidney cells., The cdc42 GTP-Binding Protein function was shown to be required for PTEN localization in leukocytes., Results describe a quantitative model of allosteric regulation of the Wiskott-Aldrich syndrome protein (WASP) by the Rho GTPase Cdc42., Silencing of Cdc42 by small interfering RNA induced massive apoptosis, indicating that tumor cell survival requires a minimal Cdc42 activity., Activation of small RhoGTPases is a key step in the mechanism of epithelial mesemchymal transdifferentiation and likely to be a contributor to tubulointerstitial fibrosis., a Cdc42 mutant is specifically activated by intersectin, binding of Cdc42 localizes Pak2 to the endoplasmic reticulum, where autophosphorylation alters association of the two proteins, the signals induced by integrin alpha6beta1 modulate at the level of PI3K and Cdc42 activity to allow platelets to actively form filopodia, The two unique glutamates in Cdc42 and basic region of WASp generate favorable electrostatic steering forces that control the accelerated WASp-Cdc42 association reaction., Cdc42 induces activation loop phosphorylation and membrane targeting of mixed lineage kinase 3, Cdc42 regulates AJ permeability by controlling the binding of alpha-catenin with beta-catenin and the consequent interaction of the VE-cadherin/catenin complex with the actin cytoskeleton., Results suggest that ABCA1 transduces signals from apolipoprotein A-I (apoA-I) by complexing and activating Cdc42 and downstream kinases and, therefore, acts as a full apoA-I receptor., Cdc42 is a critical regulator of T cell actin dynamics, T cell receptor clustering, and cell cycle entry. Cdc42 activity in specific locations at specific times is most critical for its function in T cell activation., PIP3 and Cdc42 maintain stable polarity with a single front and a single back not only by strengthening pseudopods but also, at longer range, by promoting RhoA-dependent actomyosin contraction at the trailing edge., NFAT1, a transcription factor connected with breast cancer metastasis, is activated by Wnt-5a through a Ca2+ signaling pathway in human breast epithelial cells which was simultaneously counteracted by a Wnt-5a-induced Yes/Cdc42 signaling pathway., Cdc42 is an important downstream factor in the pathway through which PKC mediates morphological and cytoskeletal effects, Cdc42 exerts its effects on cell migration in part through its effector Ack1, which regulates p130(Cas) signaling., Rho family GTPases play a distinct role in Salmonella-induced cellular responses., These results support a model whereby the synergic bundling activity of the IRSp53-Eps8 complex, regulated by Cdc42, contributes to the generation of actin bundles, thus promoting filopodial protrusions., Complex interplay of Rho, Rac and Cdc42 in the process of EphB-mediated cell retraction-recovery responses., Maspin controls mammary tumor cell migration through inhibiting Rac1 and Cdc42, but not RhoA GTPase., We propose that increased water influx through AQP9 is critically involved in the formation of membrane protrusions, and that AQP9-induced actin polymerization is augmented by activation of Cdc42 and PKC(zeta)., Signaling to the actin cytoskeleton by low and high concentrations of resveratrol may be differentially regulated by Rac and Cdc42., OxPAPC promoted novel interactions between focal adhesion and adherens junction complexes via paxillin and beta-catenin association, which was critically dependent on Rac and Cdc42 activities., Efficient phagosomal maturation and the subsequent eradication of ingested microbes in human neutrophils is dependent on a strictly regulated Cdc42 pathway., Results of this study suggest that the Rho-family GTPases are required for efficient invasion of HeLa cells by GBS., C. jejuni invade host target cells by a unique mechanism and the activation of the Rho GTPase members Rac1 and Cdc42 plays a crucial role in this entry process., These data suggest a mechanism whereby precise spatial guanine nucleotide exchange of Cdc42 by Dbl is dependent on functional ERM proteins and is important for directional cell migration., Results describe the neurite outgrowth multiadaptor RhoGAP, NOMA-GAP, and show that it regulates neurite extension through SHP2 and Cdc42., IQGAP1 regulates Salmonella invasion through interactions with actin, Rac1, and Cdc42, FGFR-mediated phosphorylation of ephexin1 enhances the guanine nucleotide exchange activity toward RhoA without affecting the activity to Rac1 or Cdc42., Cdc42 signaling contributes to immune escape of cancer, These results indicate that START-GAP3/DLC3 has characteristics similar to other START-GAPs and the START-GAP family seems to share common characteristics., signaling pathway by which G(i)-coupled receptor specifically induces Rac and Cdc42 activation through direct interaction of Gbetagamma with FLJ00018., DOCK2 and DOCK9 specifically recognize Rac2 and Cdc42 through their switch 1 as well as beta2-beta3 regions and the mode of recognition via switch 1 appears to be conserved among diverse Rac-specific DHR-2 GEFs, Theses results support a novel role for FPR stimulation in enhancing intestinal epithelial cell restitution through PI3K-dependent activation of Rac1 and Cdc42., Silencing Cdc42 blocks activation of EGFR and Src induced by Ca2+ depletion, resulting in a reduction in E-cadherin degradation, role of RHO GTPases RAC1 and CDC42 in PGE(2)-mediated migratory responses of extravillous trophoblast cells, Bioinformatics and functional analyses revealed a spatially compartmentalized Rac/Cdc42 signaling network that operates in conjunction with multiple guanine-nucleotide exchange factors and GTPase-activating proteins to control neurite formation, LKB1 interacts only with active form of cdc42 and PAK, but not with inactive cdc42. Taken together, these results show that LKB1 is a critical mediator of the NSCLC polarity program in lung cancer cells through a novel LKB1-cdc42-PAK pathway., TGFbeta1 stimulates CCN2 expression in human gingival fibroblasts through a RhoA-independent, Rac1/Cdc42-dependent mechanism, Data show that Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling., analysis of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis, The purpose of this study was to characterize the significance of Rho processes in the cellular cytoskeleton., structural analysis of the influence of effector proteins on the signaling-active state of the small GTPase Cdc42, These findings suggest a novel MUC1-Src-CrkL-Rac1/Cdc42 signaling cascade following ICAM-1 ligation, through which MUC1 regulates cytoskeletal reorganization and directed cell motility during cell migration., Data suggests that actin polymerization and cdc42 are required for activation of integrin alpha2beta1, but not alpha(IIb)beta3, thereby critically regulating platelet adhesion to and activation by collagen., components of small GTPase signal transduction pathways may be directly targeted by alpha-synuclein oligomers which potentially leads to signaling deficits and neurodegeneration., salmonella enterica SopB colocalizes with activated Cdc42 near the plasmalemma, but there was no evidence that SopB alone can alter Cdc42 activity, The exocyst subunits Sec3 and Sec8 interact with the polarity protein IQGAP1 and that this interaction is triggered by active Cdc42 and RhoA, which are essential for matrix degradation., strongly activated in HTLV-1 infected T cell lines derived from HAM/TSP patients., Fanconi anemia group A proteins influence BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway., Cdc42 was found to be overexpressed with high incidence (60%) in colorectal cancer samples, and this expression was associated with silencing of ID4 with statistical significance (p<0.05)., 1) PAK plays a required role in hyperosmotic signaling through the PI3K/pTEN/Cdc42/PP2Calpha/p38 pathway, and 2) PAK and PP2Calpha modulate the effects of this pathway on focal adhesion dynamics., IpaC could not be shown to interact directly with Cdc42, a host GTPase closely tied to Shigella invasion., Nm23-H1 can negatively regulate cell migration and tumor metastasis by modulating the activity of Cdc42 and possibly other Rho family members through interaction with Dbl-1, In melanoma, expression of activated Cdc42 induces a mesenchymal-amoeboid transition and increases cell invasion., levels of GTPase Cdc42 could be associated with slow growth of BCL2 overexpressing immortalized breast cell line, the interaction of the RAGE cytoplasmic domain with Dia-1 is required to transduce extracellular environmental cues evoked by binding of RAGE ligands to their cell surface receptor, resulting in Rac-1 and Cdc42 activation and cellular migration, EB1 is controlled by c-Myc, RhoA, and CDC42, which have all been linked to hepatocellular carcinoma (HCC) malignancy., Cdc42 was necessary for the growth and maintenance of already established lymphomas in vivo. These data open perspectives for new therapeutic strategies by revealing a mechanism of regulation of anaplastic large cell lymphoma cell growth through Cdc42, Cdc42 regulates epithelial tissue morphogenesis by controlling spindle orientation during cell division., study found Vibrio VopS could act to covalently modify a conserved threonine residue on Rho, Rac & Cdc42 with AMP; resulting AMPylation prevented interaction of Rho GTPases with downstream effectors, inhibiting actin assembly in the infected cell, Cdc42 has a novel role in controlling centrosome organization in unstimulated cells in addition to its known function as a regulator of centrosome reorientation in stimulated cells., Data demonstrate that spindle orientation in adherent cells is regulated by two distinct pathways downstream from Cdc42 and uncovers a novel role of the Cdc42-PAK2-betaPix-actin pathway for this mechanism., Cdc42 activity is impaired in beta1 integrin-deficient T cells that form conjugates with antigen-presenting cells but is partially restored in the context of an antigen-specific synapse., The higher exchange activity of ITSN1L towards the GDP-bound conformation of Cdc42 could represent an evolutionary adaptation of this GEF that ensures nucleotide exchange towards the formation of the signalling-active GTP-bound form of Cdc42., an unexpected TGF-beta signaling independent role for TbetaRIII in activating Cdc42, altering the actin cytoskeleton and reducing directional persistence to inhibit random migration of both cancer and normal epithelial cells, Data reveal a multicomponent kinase signaling pathway downstream of integrin-matrix interactions and Cdc42 activation involving PKCepsilon, Src, Yes, Pak2, Pak4, B-Raf, C-Raf and ERK1/2 to control EC lumen formation in 3D collagen matrices., A model where IQGAP1 serves as a phosphorylation-sensitive conformation switch to regulate the coupling of cell growth and division through a novel CDC42-mTOR pathway., T-cadherin transcriptionally activated Rac1 and Cdc42., Results show that this unique and specific bacterial entry process is dependent on the cooperation and activation of Rho family GTPase Cdc42, PI3K, and Akt., CSF-1-induced WASP activation was fully Cdc42-dependent., Results suggest that adiponectin promotes the migration activities of endothelial progenitor cells mainly through PI3-kinase/Cdc42/Rac1., ITSN-2L, a guanine nucleotide exchange factor for Cdc42, regulates different steps of caveola endocytosis in ECs by controlling the temporal and spatial actin polymerization and remodeling sub-adjacent to the plasma membrane., In summary, these results suggest that actin, likely modulated by the GTPases RhoA and Cdc42 and by bacterial proteins, is involved in the formation of the typical parasitophorous vacuole., Rac1 and Cdc42 signaling has a role during early herpes simplex virus type 1 infection of keratinocytes, Recycling endosome trafficking to the Golgi complex through a pathway involving Src-family kinases, Cdc42, and Rab11a plays a general role in death signaling by mediating regulated changes in Golgi dynamics., Cdc42-GDP can inhibit TC21 activation by RasGRF GEFs, demonstrating that Cdc42 negatively affects the functions of RasGRF GEFs irrespective of the GTPase being targeted., phosphorylation of Cdc42 at Ser-71, exemplarily induced by epidermal growth factor, reduces Clostridium difficile toxin A-induced changes in the intestinal barrier function., Internalization of DENV-2 into endothelial cells requires viral induction of dynamic filopodia regulated by Rac1 and Cdc42 cross-talk and myosin II motor activities., Activation of Cdc42 GTPase through p210(Bcr-Abl) tyrosine kinase signaling in CML cells contributes to defects in SDF-1alpha-chemotactic response due to desensitization of the actin polarization signal required for directional migration., HS could regulate fusion via fine tuning of RhoA and Cdc42 activities., Cdc42 regulates the uropod through CD11b signaling to maintain polarity in migrating neutrophils., Cell division cycle 42 (CDC42) showed a difference between follicular cells from follicles leading to a pregnancy or developmental failure., These results suggest that the novel gene, Kenae/CCDC125, acts as a regulator of cell motility through RhoA, Rac1 and cdc42., Data identify a novel signaling pathway in the endocrine L cell, whereby Cdc42 regulates actin remodeling, activation of the cannonical 1/2-ERK1/2 pathway and PAK1, and GLP-1 secretion in response to insulin., RhoA plays an antagonistic role to Rac1/Cdc42 in the control of mammary epithelial acinar morphogenesis., this work does not conform to current views that the inverse-BAR domain or Cdc42 controls IRSp53 localization but provides an alternative model of how IRSp53 is recruited (and released) to carry out its functions at lamellipodia and filopodia., MT1-MMP and Cdc42 co-regulate tumor cell invasion in 3D collagen matrices., expression of several highly significant cancer related genes require the activities of Rac1 and/or Cdc42 which may also play a critical role in cellular transformation, Impaired NK-cell migration in WAS/XLT patients, Endothelial lumen signaling complexes control 3D matrix-specific tubulogenesis through interdependent Cdc42- and MT1-MMP-mediated events., TSC2 has a role in controlling cell polarity and migration by regulating CDC42 and RAC1 activation, These results suggest that plasma membrane sphingomyelin is required for targeting of Helicobacter pylori VacA to membrane rafts important for subsequent Cdc42-dependent pinocytic cellular entry., This study demonstrates that controlled regulation of PAK4 is required for apical junction formation in lung epithelial cells and highlights potential cross-talk between two Cdc42 targets, PAK4 and Par6B., Cdc42 may influence endocytic membrane trafficking by regulating the formation and activity of the Toca-1/N-WASP complex., Cdc42, by inhibiting GSK-3beta, markedly improves the angio-architecture and lumenization of neovessels induced by VEGF., Activation of Rac1 and Cdc42 correlated with stabilized barrier functions in intestinal epithelium., Expression of constitutively active Cdc42 decreasea RhoA-GTP level in human lung microvascular lymphatic endothelial cells., Important role played by Cdc42 in CCL19-induced migration and invasion of squamous cell carcinoma of the head and neck cells., Cdc42 was found to be necessary for breast cancer cell invasion but dispensable for cell migration, Data show that miR-185 is a negative regulator of RhoA and Cdc42 and their cellular activities, and could inhibit proliferation and invasion of colorectal cancer cells., miR-137 is frequently down-regulated in gastric cancer and is a negative regulator of Cdc42., Cdc42-dependent formation of the ZO-1/MRCKbeta complex at the leading edge controls cell migration., Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration, Cdc42 were down-regulated on the protein level.The formation of filopodia, which requires Cdc42, was inhibited in miR-206 transfected cells, even under EGF stimulation, The Cdc42-APC interaction induces localization of both APC and mutant APC and may thus play a direct role in the functions of these proteins., These results demonstrate an important role for FGD1/Cdc42 signaling in human mesenchymal stem cells osteogenesis., Interaction of the Salmonella Typhimurium SopB with host Cdc42 is involved in intracellular replication., HIV-1 activates Cdc42 and induces membrane extensions in immature dendritic cells to facilitate cell-to-cell virus propagation., Aberrant expression of Annexin A2 and Cdc42 play a role in carcinogenesis, differentiation and metastasis of esophageal squamous cell carcinomas., Multiple factors confer specific Cdc42 and Rac protein activation by dedicator of cytokinesis (DOCK) nucleotide exchange factors., endogenous Cdc42 could exert a negative regulatory influence on intrinsic migration/invasion and some potentially relevant changes in phosphorylation of PKCdelta, Erk1/2, and PKA of some aggressive breast cancer cells, Mutation of threonine(35) leads to loss of conformational freedom in the Cdc42 Switch I signaling pathway that could affect effector-regulatory protein interactions., Demonstrate a role for RasGRF1/2 as negative regulators of Cdc42 activation, suppressing tumor cell movement, cytoskeletal dynamics and cell transformation., Cdc42 enhances the resistance of colon cancer cells to several antitumor drugs., Phosphatase and tensin homologue deleted on chromosome 10 may influence apoptosis in colorectal epithelium through Cdc42 signalling, thus providing a regulatory framework for both polarised growth and programmed cell death., Burkholderia cenocepacia perturbs actin architecture by inactivating Rho family GTPases, particularly Rac1 and Cdc42., CDC42 may have a key role in ameloblastoma neoplastic epithelial cell phenotype determination, as well as in variant and subtype determination., Estrogen enhances the drug resistance in breast cancer cells, possibly by enhancing Cdc42 expression., The guanine nucleotide exchange factors RhoGEF6 and RhoGEF7 were necessary for Cdc42 activation within the NK cell immunological synapse., delta-catenin facilitated invasion of lung cancer cells by upregulating the mRNA and protein levels of cdc42, Data suggest a potential therapeutic role for curcumin in inducing Cdc42-mediated inhibition of invasion of lung cancer cells., silencing Cdc42 reduced influenza A virus replication, whereas silencing ARHGAP21 increased the virus replication., Using synthetic derivatives of the enteropathogenic Escherichia coli guanine-nucleotide exchange factor (GEF) Map, authors discover that Cdc42 GTPase signal transduction is controlled by the interaction between Map and F-actin., analysis of the SopB GTPase binding domain in complex with Cdc42 shows for the first time that SopB structurally and functionally mimics a host guanine nucleotide dissociation inhibitor by slowing cdc24 nucleotide exchange., Data support the CDC42 gene as a candidate schizophrenia susceptibility gene., Modulation of Cdc42 signaling through FAK by receptor activation underlies changes in growth cone motility., study demonstrated that LMP1 acts through its transmembrane domains to preferentially induce Cdc42 activation in various types of epithelial cells, including NPC cells., FMNL2 is a novel elongation factor of actin filaments that constitutes the first Cdc42 effector promoting cell migration and actin polymerization at the tips of lamellipodia., several Rho family small GTPases activate PI3K by an indirect cooperative positive feedback that required a combination of Rac, CDC42, and RhoG small GTPase activities, studies implicate Cdc42 in Ras-driven tumor growth and suggest that targeting Cdc42 is beneficial in Ras-mediated malignancies, endothelin 1 stimulates trophoblast cell migration through GTP binding protein CDC42 activation, overexpression of Dsg3 results in a remarkable increase of Rac1 and Cdc42 activities, Cdc42 controls actin depletion at the immunological synapse., Epithelial junction formation and morphogenesis require a dual activity complex, containing SH3BP1 and CapZ, that is recruited to sites of active membrane remodeling to guide Cdc42 signaling and cytoskeletal dynamics., Arhgef15 acts as an endothelial cell-specific GEF to mediate VEGF-induced Cdc42 activation and potentiate RhoJ inactivation, thereby promoting actin polymerization and cell motility., Inhibition of S1P3 receptors prevented E2-induced activation of Cdc42, supporting the important role of the S1P receptor in E2 signaling., The transient Cdc42 depletion was sufficient to decrease experimental lung metastases, which suggests that its role in endothelial attachment is important for metastasis., Data suggest that microRNA 137 influences cell proliferation via regulation of expression of CDC42 and CDK6 (cyclin-dependent kinase 6); expression of microRNA 137 in lung cancer cells downregulates CDC42/CDK6 and induces G1 cell cycle arrest., Constitutively active Cdc42 or NFAT1 mutants fully restore the impaired expansion of SWAP-70-like adapter of T cells (Def6)-deficient CD8+ T cells., DOCK7 binds to the RAGE cytoplasmic domain and transduces a signal to Cdc42., Cdc42 interacts with the exocyst complex to promote phagocytosis., these results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation., Prenylated and palmitoylated brain Cdc42 did not interact with RhoGDIalpha., The aim of this study was to examine the expression of ERM (ezrin, moesin) and Rho (RhoA, RhoB and Cdc42) proteins in breast cancer (BC) patients., Silencing of LRP1B altered the expression of focal adhesion complex-associated proteins, and Cdc42/RhoA activities., Cdc42 differentially modulate cigarette smoke-induced airway cell migration through p120-catenin-dependent and -independent pathways, Prom2 protrusions primarily localize to lipid rafts and recruit cholesterol into protrusions and away from caveolae, leading to increased phosphorylation of caveolin-1, which inhibits Cdc42-dependent endocytosis, Cdc42 knockdown were c-Cbl-dependent was provided by transducing Cdc42 knockdown cells with secondary c-Cbl shRNAs before transplantation., Negative pressure wound therapy activates Cdc42 pathway facilitating migration to accelerate wound healing., The transcription of cdc42, a kind of Rho GTPase which plays a key role in actin polymerization, was reduced by down-regulated B antigen expression., Data show that macrophages on gastric and colorectal cancer cells migration through epidermal growth factor receptor and phosphorylation of Akt, c-Src and ERK1/2, and led to an increase of RhoA and Cdc42 activity., Acute ischemic stroke was associated with reduced levels of Cdc42 protein in peripheral lymphocytes., The action of DOCK7 in vivo may involve the coordinated integration of Cdc42/Rac1 signaling in the context of the membrane recruitment of a DOCK7 guanine nucleotide exchange factor (GEF) complex., activated Rac1/Cdc42 is a vascular regulator of tumor angiogenesis and that it may reduce stability of the p53 protein to promote VEGF expression by enhancing p53 protein ubiquitin, These results indicate that Neisseria meningitidis selectively exploits the epithelial microenvironment in order to protect itself from LL-37 via a RhoA and Cdc42 mediated mechanism., Active Rho GTPase Cdc42 can greatly enhance colorectal cancer cell SW480 to spread, migrate, and invade, which may contribute to colorectal cancer metastasis., Study determined that p16-stimulated cell migration requires the Cdc42 GTPase., a significant role of S79 in PAK1 activation and a noval mechanism of the CRIB-mediated interaction of PAK1 with Cdc42 and Rac, Expression of Cdc42 (and Asef) together was associated with tubular injury with 100% specificity., Data indicate mTOR kinase-independent function and mechanism of Rictor in the regulation of neutrophil chemotaxis, and suggest that the small Rho GTPases Rac and Cdc42 serve as downstream effectors of Rictor to regulate actin assembly., Differential expression of miR-195 in esophageal squamous cell carcinoma and miR-195 expression inhibits tumor cell proliferation and invasion by targeting of Cdc42, Rs2349775 (NXPH1) and rs17837965 (CDC42) were associated with diarrhoea and constipation predominant irritable bowel syndrome, respectively, in two independent cohorts., findings demonstrate that dual lipidation of Cdc42-palm represents an important regulator of morphogenic signalling in hippocampal neurons., Cdc42 overexpression induces hyperbranching in the developing mammary gland by enhancing cell migration., a possible role of GPR97 in lymphatic remodeling, These results indicate that Wnt5b is involved in the migration ability of OSCC cells through active Cdc42 and RhoA., we show that cIAP1 regulates TNF-induced actin cytoskeleton reorganization through a cdc42-dependentpathway, Our observations suggest that ITSN1 is an important general regulator of Cdc42-, Nck- and N-WASP-dependent actin polymerisation, Invasion of host cells, which occurs at a low frequency, does not seem linked to Rac1 activation by Vibrio parahaemolyticus VopC, but instead appears to require CDC42., Our data indicate that injured keratinocytes induce MMP-1 expression through ERK activation, and this process is negatively regulated by Cdc42 activity., Dbl3 drives Cdc42 signaling at the apical margin., A FRET-based Cdc42 biosensor was used to examine the effects of the rigidity of three-dimensional collagen matrices on spatiotemporal activity of Cdc42 in endothelial colony forming cells., Listeria monocytogenes emply a novel mechanism of bacterial spread involving pathogen-induced downregulation of host Cdc42., IRSp53 adopts a closed inactive conformation that opens synergistically with the binding of human Cdc42 to the CRIB-PR and effector proteins, such as the tumor-promoting factor Eps8, to the SH3 domain., YES kinase as a proximal glucose-specific signal in the Cdc42-signaling cascade., The human cdc42 gene is a direct target of miR-204., CCH-mediated inhibition of NHE3 activity is not dependent on clathrin and involves lipid rafts and requires Cdc42., Increased miR-224 diminished Cdc42 and SMAD4 expressions at both the protein and mRNA levels and inhibited the formation of actin filaments., CDC42 is activated by phosphatidylinositol 5-phosphate, regulating actin dynamics and cell invasion., These findings show that overexpression of PODXL enhanced invadopodia formation and tumor metastasis by inducing Rac1/Cdc42/cortactin signaling network., Findings suggest that Wnt5a enhances cell migration through activation of Cdc42 and inactivation of RhoA in human corneal endothelial cells., inhibiting Cdc42 function impairs vessel co-option and converts pericytes to a phagocytic/macrophage-like phenotype, thus favoring an innate immune response against the tumor., CDC42 has a crucial role in senescence-associated inflammation and atherosclerosis., Findings indicate that tricellular contacts play crucial roles in regulating the actomyosin-mediated apical junctional complex tension through the tricellulin-Tuba-Cdc42 system., Cdc42Hs binds to the effector domain of PAK3, Cdc42 may promote breast cancer cell migration and invasion by inhibiting ERK5 phosphorylation and ERK5 expression may be inversely correlated with the progression of some breast tumors., Snail regulates the motility and invasiveness of oral cancer cells via RhoA/Cdc42/p-ERM pathway., Silencing of CDC42 decreased expression of N-myc in BE(2)-C and BE(2)-M17 cells., Cdc42 and the formins diaphanous and DAAM play pivotal roles in heart lumen formation through the spatiotemporal regulation of the actomyosin network., metformin impairs Rho GTPases signaling to induce apoptosis via JNK pathway, The homeostatic function of miR-18a within the miR-17-92 cluster in colorectal cancer cells may be achieved through suppression of CDC42 and the PI3K pathway., Cdc42 overexpression significantly improved the ability of cervical cancer cells to migrate possibly due to improved pseudopodia formation., Suggest that the combined aberrant expression of miR-195 and Cdc42 mRNA can serve as a promising unfavorable prognostic biomarker in esophageal squamous cell carcinoma., Cdc42 and its specific guanine nucleotide-exchange factor (GEF), Tuba, localize to linear invadosomes, and both are required for linear invadosome formation, MiR-25, by targeting CDC42, is an important regulator in NSCLC., Results provide novel evidence that low expression of SLIT2 correlates with poor prognosis and promotes metastasis in ESCC, which may be regulated by the Cdc42-mediated pathways., HIV-1 Tat inhibits phagocytosis by preventing the recruitment of Cdc42 to the phagocytic cup., PAK4 phosphorylates Par6B at Ser143 blocking its interaction with Cdc42., Cdc42 is implicated in the CFTR biosynthesis and processing, maintaining the level of Cdc42 and its effectors in cells, tumor progression can be controlled., Study shows that activation of CDC42 in HeLa cells causes increased radiosensitivity, cells arrest in G2/M and reduced survival. These results complete the understanding of the signaling roles of CDC42 in maintaining genomic stability and integrity., COPI tubular transport complements cisternal maturation in explaining how anterograde Golgi transport is achieved, and that bidirectional COPI transport is modulated by environmental cues through CDC42., This study showed that cdc42 messenger RNA levels were significantly downregulated specifically in deep layer 3 pyramidal cells in patient with schizophrenia., In marked contrast to invadopodia, this degradation does not require the action of Src kinase, Cdc42 or Dyn2. Rather, inhibition of Dyn2 causes a marked upregulation of stromal matrix degradation, Rich1 negatively regulates the epithelial cell cycle, proliferation and adhesion by CDC42/RAC1-PAK1-Erk1/2 pathway., Robo1 promoted cell division cycle 42 (Cdc42) expression in HUVECs, and a distorted actin cytoskeleton in HUVECs was observed when Robo1 expression was suppressed. In conclusion, Robo1 promoted angiogenesis in HCC mediated by Cdc42., IQGAP1 and its two isoforms regulate the actin-cytoskeleton alone and with their binding partners, Rac and Cdc42, thereby controlling diverse cellular processes, such as cell migration and adhesion. (Review), The structural details of the cdc42 protein have been described that determine its recognition by the bacterial c3 exoenzyme., PAK4 binding to cell-cell junctions is dependent on Cdc42., Ketorolac has a novel pharmacologic activity conferred by the R-enantiomer and R-ketorolac achieves sufficient levels in the peritoneal cavity to inhibit Rac1 and Cdc42, contributing to the observed survival benefit in women who received ketorolac, FMNL3 interacts with Cdc42 and RhoJ, two Rho family GTPases known to be required for lumen formation. FMNL3 and RhoJ are concentrated at the early apical surface, or AMIS, and regulate the formation of radiating actin cables from this site., Results suggest that the role of polypyrimidine tract binding protein 1 (PTBP1) in tumorigenesis may be partly mediated by its regulation of cdc42 GTP-binding protein (CDC42) alternative splicing and CDC42-v2 might function as a tumor suppressor., CDC42 independently regulated the antitumor effects of miR-137 in human hepatocellular carcinoma., Authors conclude that a transient interaction between Cdc42 and GRAF1 drives endocytic turnover and controls the transition essential for endosomal maturation of plasma membrane internalised by this mechanism., MARCKS upregulation increases vascular smooth muscle cell motility by activation of Rac1 and Cdc42, promoting neointima formation., Results show that the activation of cdc42 GTP-binding protein (Cdc42) is a process of conformational changes., CDC42 is a key regulator involved in regulating the proliferation, migration and invasion of gastric cancer., Data indicate enantiomer selective interaction of R-naproxen and R-ketorolac with Rho family GTPases Rac1 and Cdc42., we discovered distinct predictive performance of Rac1 and Cdc42 depending on the migration modes, indicating that Rac1 and Cdc42 contribute to persistent and random migration, respectively, Chemotactic steering and de novo polarization are both directed by locally excitable Cdc42 signals in neutrophils., Data suggest LPA (lysophosphatidic acid; acting via LPAR1) and endothelin activate Cdc42, concurrent with biphasic decrease in Rac1 activity, differential effects on RhoA; LPA/endothelin stim. leads to remodeling of invadosomes in melanoma cells., Shp2 also mediates Cdc42 repression, and HDAC6 inhibition or co-suppression of ERK/myosin II promotes normal epithelial lumen phenotype without increasing Cdc42 activity., Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator., miR-1 bound both MALAT1 and cdc42 3'UTR directly. Further study showed that MALAT1 induced migration and invasion of breast cancer cells while reduced the level of cdc42.,
OFFICIAL_GENE_SYMBOL CDC42,
OMIM_DISEASE Takenouchi-Kosaki syndrome,
SP_COMMENT enzyme regulation:Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase., function:Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Causes the formation of thin, actin-rich surface projections called filopodia., similarity:Belongs to the small GTPase superfamily. Rho family., similarity:Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily., subunit:The GTP-bound form interacts with CCPG1 (By similarity). Interacts with CDC42EP1, CDC42EP2, CDC42EP3, CDC42EP4, CDC42EP5, CDC42SE1, CDC42SE2, PARD6A, PARD6B and PARD6G (in a GTP-dependent manner). Interacts with activated CSPG4 and with BAIAP2. Interacts with Zizimin1/DOCK9 and Zizimin2/DOCK11, which activate it by exchanging GDP for GTP. Interacts with NET1 and TCGAP/SNX26. Part of a complex with PARD3, PARD6A or PARD6B and PRKCI or PRKCZ.,
ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)(RAC1) ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)(RAC1) Related Genes Homo sapiens
CHROMOSOME 7,
CYTOBAND 7p22,
ENSEMBL_GENE_ID ENSG00000136238,
GENERIF_SUMMARY protein interaction mapping with guanine nucleotide exchange factor, Tiam1, Our findings indicate that different signal cascades resulting in the activation of Rac1 ...can modulate the exocytotic process of neuroendocrine cells., Rac1 is required for capillary lumen formation by vascular endothelial cells in three-dimensional extracellular matrices, role for the small GTPases Rac1 in the generation of skeletal muscle tumors., Interaction between p21-activated protein kinase and Rac during differentiation of HL-60 human promyelocytic leukemia cell, Rac1 generates reactive oxygen species through beta-amyloid signaling, Rac1 play essential role in regulating the formation of dendritic processes by dendritic cell, proteasomal degradation of cytotoxic necrotizing factor 1-activated rac1, These results demonstrate that Rho family small GTPases RhoA, Rac1 and Cdc42 are novel signal transducers for SP-stimulated IL-8 expression., Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck, Data show that arsenic trioxide induces activation of the small G-protein Rac1 and the alpha and beta isoforms of the p38 mitogen-activated protein (MAP) kinase in several leukemia cell lines., Rac1 and Cdc42 are activated independent of RhoG, role in pathway that promotes urokinase plasminogen activator mRNA stability in invasive breast cancer cells, mechanism of IL-2-activated Rac1 regulation of Akt-dependent cell survival in NK cells, DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines, Cdc42/Rac1-dependent activation of the p21-activated kinase (PAK) regulates human platelet lamellipodia spreading., RAC1-controlled cascades promoting lamellar protrusion are independent of MAPK activity and partially down-regulated by p-JNK., Rac/Cdc42-dependent activation of MAPK/ERK is a critical event in the immediate phagocytic response of PMNs to microbial challenge, Adenoviral-mediated expression of the constitutively active allele of Rac1 in human umbilical vein endothelial cells results in mitochondrial oxidative stress with induction of biochemical, molecular, and morphological features of senescence., The requirement for polyamines for intestinal epithelial cell migration is mediated through this protein., Data show that inhibition of endogenous RhoA, Rac1, and Cdc42 by their respective dominant negative mutants inhibits neurotensin-induced interleukin-8 protein production and promoter activity., Rac1 and superoxide play crucial roles in the regulation of expression of cell adhesion molecules in endothelial cells, TRE17 coprecipitated specifically with the active forms of Cdc42 and Rac1 in vivo. TRE17 is part of a novel effector complex for Cdc42 and Rac1, potentially contributing to their effects on actin remodeling., The beta2 integrin-triggered relocalization of Rac1 to the cytoskeleton was enabled by a PI 3-kinase-induced dissociation of Rac1 from LyGDI, AIF-1 binds and polymerizes F actin and also regulates Rac1 activity and vascular smooth muscle migration, evid,ence that the small GTPases RhoA and Rac1 but not Cdc42, are directly associated with Tyk2 and PI3-K in an uPA/uPAR-dependent fashion and are necessary to mediate the uPA/uPAR-directed migration via the Tyk2/PI3-K signalling complex in human VSMC, an enhanced activation of Rac1 in primary human schwannoma cells, Rac1-dependent pathways that participate in Src-induced cell transformation are regulated by Vav2 and Tiam1, Rac1 has a role in thrombospondin 2 regulation of cell growth via redox-dependent signaling, C-terminal, hypervariable domain of Rac1 encodes two distinct binding motifs for signaling proteins and regulates intracellular targeting and differential signaling in a unique and non-redundant fashion, Rho protein regulates the tyrosine phosphorylation of FAK through translocation from the nucleus to the membrane, Rac1, but not not Rac2 has a role in the human NADPH oxidase complex, direct activation of Cdc42 and Rac1 by invasive Salmonella is a prerequisite of Salmonella-mediated death of U937 cells., Rac1 and RhoA bind to adherens junctions and myosin light chain during formation of capillary vascular network, alternative splicing of Rac1 leads to a highly active Rac variant that differs in regulation and downstream signaling, analysis of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1, bFGF- and NGF-induced phosphorylation of p85 betaPIX mediates Rac1 activation, which in turn regulates cytoskeletal reorganization at growth cones, but not translocation of the PIX complex., ROS such as superoxide and H(2)O(2) derived from Rac1-activated NADPH oxidase mediate TNF-alpha-induced MCP-1 expression in endothelial cells, cleavage of CD44 catalyzed by ADAM10 is augmented by the intracellular signaling elicited by engagement of CD44, through Rac1-mediated cytoskeletal rearrangement, and suggest that CD44 cleavage contributes to the migration and invasion of tumor cells, Alternatively spliced Rac1b is able to bind the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner., data identified Rac1 as a key intermediate in Yersinia enterocolitica invasin-triggered IL-8 synthesis, Rac1 activates Dbs at the pleckstrin homology domain, Expression of either dominant-negative or constitutively active forms of RAC1 prevented lamellipodial formation., alterations of rac1 gene may contribute to tumorigenesis and/or metastasis, Nef binds the DOCK2-ELMO1 complex to activate rac and inhibit lymphocyte chemotaxis, down-regulation of the activity of this GTPase is a requirement for the regulation of T cell morphology and motility, agonist-induced internalization of thromboxane A2 receptor beta was regulated by Nm23-H2 through modulation of Rac1 signaling, rhoA and rac-1 participate in cell sensitivity to mechanical strain and lead to the modulation of the Erk pathway., Data suggest that hyaluronan-CD44 interaction with Rac1-protein kinase N gamma plays a pivotal role in phospholipase C gamma1-regulated calcium signaling and cortactin-cytoskeleton function required for keratinocyte cell-cell adhesion and differentiation., cross-talk between Rac and Cdc42 GTPases regulates generation of reactive oxygen species, lamellipodial protrusion in smooth muscle cells can be regulated by waves of Rac1 activation, Rac-1 overexpression is a frequent occurrence in oral squamous cell carcinoma (OSCC), highlighting the involvement of GTPase elements in the neoplastic growth of OSCC., activation of Rac1 leads to HIV-LTR trans-activation, mediated through TIRAP. Rac1 and TIRAP are important in TLR4 activation of HIV replication, activated by HIV Env-coreceptor interactions during HIV-induced membrane fusion and cell-cell fusion, Data support a mechanism by which active Rac1 promotes lymphoma cell survival and inhibits apoptosis in response to cancer chemotherapy drugs., a G protein-coupled receptor encoded by HHV8 activates Rac1, which links the viral GPCR to transcription factor activation, novel phosphorylation-dependent function of Bam32 in regulating Rac1 activation and actin remodeling., Both Cdc42 & Rac1 control the transport of essential immunostimulatory molecules to the DC surface. Cdc42 and Rac1 signaling controls DC morphology and conditions DCs for efficient CD8(+) T cell stimulation., Coordination of both RhoA and Rac1 activity contributes to bronchial epithelial wound repair mechanisms in vitro., Our results suggest that Racl may be involved in angiogenesis by controlling the expression of angiogenesis-related factors., the activity of Rac1 is suppressed during cytokinesis, increasing at the plasma membrane of polar sides before the abscission of the daughter cells in both HeLa and Rat1A cells, Rac1 activation is inhibited by SPRY2, activation of Rac1 amplifies the signaling activity of stabilized/mutated beta-catenin by promoting its accumulation in the nucleus, and synergizing with beta-catenin to augment TCF/LEF-dependent gene transcription, roles for Rac1 in early signal transduction and cytoskeletal rearrangement of T lymphocytes responding to chemokine., Rap1 promotes cell spreading by localizing a subset of Rac GEFs to sites of active lamellipodia extension, The antagonistic roles of RhoA and Rac1 in cell motility/invasion and cytoskeletal organization in breast cancer may be due to their concerted action on NHE1 activity as a convergence point., ANP is a novel endogenous activator of endothelial Rac1., Rac1, PI3 kinase, and Akt3 have roles in an anti-apoptotic pathway triggered by ALS2 that antagonizes SOD1 mutant-induced motoneuronal cell death, that Rac 1 activation accelerates the wound healing process and is associated with more efficient angiogenesis at the wound site., isoprenylcysteine carboxylmethyltransferase regulates Rac1 activity by controlling the interaction of Rac1 with RhoGDI through TNFA, a specific cross-talk between TGF-beta1 and fibronectin-binding integrin signal pathways leads to the activation of c-Src/Rac1/actin-organization, leading to changes in cell cycle regulator levels in hepatoma cells, Rac1b, a splicing variant of Rac1, stimulates cell cycle progression and cell survival in pathways involving NF-kappaB., TrioN, a Dbl family GEF, activates Rac1 by facilitating GTP binding to, as well as stimulating GDP dissociation from, Rac1, Rac1 plays a critical role in maintaining the surface expression of PAR1 and the responsiveness to thrombin in vascular smooth muscle cells, Data suggest that ICAM-1 gene induction by TNFalpha and IL-6 is mediated mainly via NFkappaB and Stat3, respectively and Rac1 appears to play a central role in modulating cytokine-induced ICAM-1 expression in endothelial cells., Activation of small RhoGTPases is a key step in the mechanism of epithelial mesemchymal transdifferentiation and likely to be a contributor to tubulointerstitial fibrosis., High frequency of overexpression of rac1 pseudogene was detected in the human brain tumors when compared with that expressed in the normal brain tissues, functional analysis of Rac1 and Rac3 using RNA interference reveals a critical role for these GTPases in the invasive behavior of glioma and breast carcinoma cells, Rac1 is required for aggregate integrity leading to thrombus formation under physiologically relevant levels of shear both in vitro and in vivo., S1P-induced recruitment of S1P1 to CEM fractions promotes PI3 kinase-mediated Tiam1/Rac1 activation required for alpha-actinin-1/4-regulated cortical actin rearrangement and EC barrier enhancement, data suggest that E. coli K1 modulates the binding of Rac1, to PAK1 during the invasion of human brain microvascular endothelial cells (HBMEC), The results suggest that oncogenic K-Ras enhances the malignant phenotype and identify the mitogen-activated protein kinase p38 as a target to inhibit oncogenic K-Ras-induced pancreatic tumor cell migration., results suggest a role for both the Rac1 and Rac3 GTPases in human breast cancer progression, Results suggest that RhoG contributes to the regulation of Rac1 activity in migrating cells., Data show that alpha6 and alpha3 integrin subunits interact with laminin 5 to increase expression of E-cadherin, and suggest that phosphoinositide 3-kinase (PI 3-kinase) activation plays a key role in this cross-talk., Rac1 facilitated the recruitment of Nox2 into the endosomal compartment and subsequent redox-dependent recruitment of TRAF6 to the MyD88/IL-1R1 complex., EGF induces ADAM10-mediated CD44 cleavage through Rac1 and mitogen-activated protein kinase activation, and thereby promotes tumour cell migration and invasion., Activated rac1 and Cdc42 are involved in the hypoxia-induced production of angiogenesis-promoting factors and tumor suppressors, and suggest that the Rho family GTPases Rac1 and Cdc42 may contribute to the hypoxia-mediated angiogenesis., activation of the c-Abl-PKCdelta-Rac1-p38 MAPK pathway in response to ionizing radiation signals conformational changes of Bak and Bax, resulting in mitochondrial activation-mediated apoptotic cell death in human non-small cell lung cancer cells, Slit2 inhibits vascular smooth muscle cell migration by suppressing small GTPase Rac1 activation., Rac1 interaction with beta-Pix (p21-activated kinase [Pak]-interacting exchange factor) is required for Rac1 activation by beta-Pix as well as for Rac1-mediated spreading, Rac1 regulates both oxidases Nox1 and Nox3 through the Nox activators, The roles of RAC1 and RAC1b in the RelB mediated transciption in 3 tumor cell lines are reported., An obligatory role for endogenous GIT2 in repression of lamellipodial extension and FA turnover by Rac1- and Cdc42-dependent signaling pathways, respectively, was demonstarted., These findings indicate for the first time that activation of geranylgeranylated proteins including RhoA and Rac1 is involved in type III GBS invasion of HBMEC and RhoA is upstream of Rac1 in GBS invasion of HBMEC., The upregulation of Rac-1 molecule might also play a role in the acquisition of dendritic cells mature phenotype., Rac1 is activated by murine leukemia virus particles in HeLa cells, Rac1 is involved in Porphyromonas gingivalis fimbria-stimulated monocytic cell adhesion to human vascular endothelium and transendothelial migration in vitro., Rac1 directly participates in Nox1 activation via interacting with Noxa1., Rac1 and Rac2 have distinct roles in regulating cell morphology, migration and invasion, but are not essential for macrophage migration or chemotaxis., These findings suggest that PI3KC2beta regulates the migration and survival of human tumor cells by distinct molecular mechanisms., Rac1 (and not Rac2) is essential for Rho and myosin activation at the trailing edge to regulate uropod function, Results suggest that ATP-mediated barrier protection is associated with cytoskeletal activation and is dependent on both Rac activation and cortactin., the polybasic motif specifically directs Rac1 to effect cytoskeletal rearrangement and cell migration by selective membrane phospholipid targeting, Both the beta4 integrin ligand-binding and cytoplasmic domains together with epidermal growth factor were required for the synergistic activation of a Rac-dependent signaling pathway that was essential for keratinocyte directional migration., The Rac is a novel angiogenic factor for HCC through the enhancement of HIF-1alpha protein stability, which provides a possible therapeutic target in the development of inhibitors of angiogenesis., Akt1 and Akt2 have opposing roles in Rac/Pak signaling and cell migration, Activation of Fn14 signaling by the ligand TNF-like weak inducer of apoptosis (TWEAK) stimulates migration and up-regulates expression of Fn14; this TWEAK effect requires Rac1 and nuclear factor-kappaB (NF-kappaB) activity., TGF-beta "cross-links" the HER2/Vav2/Rac1/Pak1/actin/actinin complex at cell lamellipodia, prolonging Rac1 activation., Taken together, these results suggest that Dock4 plays an important role in the regulation of cell migration through activation of Rac1, and that RhoG is a key upstream regulator for Dock4., Rac1 inhibition in non-metastatic or moderately metastatic cells results in inhibition of migration, whereas in highly metastatic cells Rac1 inhibition results in stimulation of migration., Rho family GTPases play a distinct role in Salmonella-induced cellular responses., Src and Rac1 have roles in focal adhesion kinase and ERK mitogenic signaling in epithelial cells, structure of the Rac1- phospholipase C (PLC)-beta2 complex reveals determinants that dictate selectivity of PLC-beta isozymes for Rac GTPases over other Rho-family GTPases, DEF6 not only activates Rho-family GTPases but also cooperates with activated Rac1 to exert its cellular function, These results suggest that ARF6 depletion or Ang II treatment are functionally equivalent and point to a role for endogenous ARF6 as an inhibitor of Rac1 activity., Localization of ezrin in adherens junctions is regulated by Rac1 in a manner involving PIPK., First step of the cell-penetrating peptide mechanism involves Rac1-dependent actin-network remodeling., The EGFR/Vav2/Rac1 axis is a crucial pathway for the acquisition of motile and invasive properties of most head and neck squamous cell carcinoma cells., RAC1 and RAC3 have opposing functions in cell adhesion and differentiation of neuronal cells., Remedial strategies in structural proteomics were used for the expression, purification, and rystallization of the VAV1/RAC1 complex., RGS3L functions as a molecular switch, redirecting Gi-coupled receptors via Gbetagamma-dimers and PI3K from Rac1 to RhoA activation., Maspin controls mammary tumor cell migration through inhibiting Rac1 and Cdc42, but not the RhoA GTPase., loss of PTEN function in human prostate cancer may specifically facilitate bone rather than other organ metastasis and suggest that Rac1, as a PTEN effector, may contribute to this metastatic tropism., Signaling to the actin cytoskeleton by low and high concentrations of resveratrol may be differentially regulated by Rac and Cdc42., Transgenic Rac1 has a critical role in axon guidance and cell migration during differentiation of the ventral telecephalon., Study identified Crk adapter proteins, Rac1 and H-Ras, but not RhoA or Cdc42 as crucial components of the Helicobacter pylori CagA protein-induced phenotype., Proinvasive activity of BMP7 through SMAD4/src-independent and ERK/Rac/JNK-dependent signaling pathways in colon cancer cells is reported., OxPAPC promoted novel interactions between focal adhesion and adherens junction complexes via paxillin and beta-catenin association, which was critically dependent on Rac and Cdc42 activities., Results of this study suggest that the Rho-family GTPases are required for efficient invasion of HeLa cells by GBS., C. jejuni invade host target cells by a unique mechanism and the activation of the Rho GTPase members Rac1 and Cdc42 plays a crucial role in this entry process., Ang-1 phosphorylates Tie-2 and its downstream effector phosphatidylinositol 3-kinase. This induces activation of one endogenous GTPase, Rac1, and inhibition of another, RhoA, the guanine nucleotide exchange factor Ost has a role in negative regulation of receptor endocytosis by the small GTPase Rac1, Adenovirus-induced activation of Rac1 enhances the ability of microtubules to "search and capture" incoming virus particles., Rac1 activates proliferation of normal fibroblasts through stimulation of c-myc phosphorylation without affecting ERK1/2 activity, expression and activity levels of Rac1 were upregulated in colorectal cancer tissues, Rac-1 GTPase-mediated reactive oxygen species production and on epidermal growth factor receptor transactivation, We found that the effects of Rac1 silencing on keratinocytes differentiation are concomitant with negative regulation of the Ser62/Thr58 phosphorylation on the transcription factor c-myc., The potential role of Rac proteins in the proliferative and invasive behavior of rheumatoid arthritis-fibroblast-like synoviocytes., Results show the requirement of the small GTPase Rac1 activity to promote Listeria internalization., These observations unravel the interplay between beta-catenin and Rac1 that is initiated by T-Ag and results in stabilization of beta-catenin and its presence in cell membrane ruffles., Rac1 GTPase is involved in regulation of platelet secretion and aggregation, Vav2 acts downstream of VEGF to activate Rac1., IQGAP1 regulates Salmonella invasion through interactions with actin, Rac1, and Cdc42, FGFR-mediated phosphorylation of ephexin1 enhances the guanine nucleotide exchange activity toward RhoA without affecting the activity to Rac1 or Cdc42., CD44 is an important regulator of HGF/c-Met-mediated in vitro and in vivo barrier enhancement, a process with essential involvement of Tiam1, Rac1, dynamin 2, and cortactin., Results suggest that Rac1 plays a critical role in signalling transduction pathways relevant to colorectal tumour progression, such as activation of Wnt signalling, inhibition of TGF-beta signalling, and enhancement of metastasis-inducing genes., A novel mechanism is proposed in which alpha6beta4 integrin signaling via Rac1, 14-3-3 proteins, and SSH family members regulates cofilin activation, cell polarity, and matrix assembly, leading to specific epidermal cell migration behavior., Rac1 signaling has a role in estrogen-induced proliferation in MCF-7 breast cancer cells, the activation of Rac1 due to the cell-cell contact plays a critical role in the transcriptional up-regulation of p27Kip1 in vascular endothelial cells., These data indicate that Rac1 activity in FEMX cells regulates cell proliferation and invasion, in part via its effect on NFkappaB, signifying Rac1 as a key molecule in melanoma progression and metastasis., Binding of Rac1, Rnd1, and RhoD to a novel Rho GTPase interaction motif destabilizes dimerization of the plexin-B1 effector domain, that Rac1 is an essential player for mediating the induction of cyclin D1 and p21(Cip1) by HRG in breast cancer cells, In primary activated CD4(+) T cells, Rac1 and Rac2 were independently required for maximal TCR-induced apoptosis., The results presented here indicate that actin reorganization through FAK/PI3-K/Rac-1 activation operates in various human cancer cell systems supporting a functional role for FAK/PI-3K/Rac1/actin signaling in controlling cell motility., 16k PRL inhibits cell migration by blocking the Ras-Tiam1-Rac1-Pak1 signaling pathway in endothelial cells, signaling pathway by which G(i)-coupled receptor specifically induces Rac and Cdc42 activation through direct interaction of Gbetagamma with FLJ00018., Theses results support a novel role for FPR stimulation in enhancing intestinal epithelial cell restitution through PI3K-dependent activation of Rac1 and Cdc42., These results suggest a novel mechanism of ANP protective effects against agonist-induced pulmonary endothelial cell barrier dysfunction via inhibition of Rho signaling by Epac/Rap1-Rac and PKA signaling cascades., Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox is critical for alpha-platelet-derived growth factor receptor-induced production of reactive oxygen species., Findings suggest that Vav3/Rac 1 signaling is an important modulator of ligand-independent AR transcriptional activity in prostate cancer progression., HBV may possibly make use of an activated Rac1 signaling pathway for increased replication and resultant metastatic effects., These results suggest that S1P(2) receptors/G(12/13)-proteins/Rho signaling pathways mediate S1P-induced inhibition of glioma cell migration., JNK-dependent activation of Rac1 ubiquitination would create a regulatory loop allowing the cell to counteract excessive activation of Rac1 GTPase, sFRP-1 can interact with Wnt receptors Frizzled 4 and 7 on endothelial cells to transduce downstream to cellular machineries requiring Rac-1 activity in cooperation with GSK-3beta, CD147, via the selective inhibition of specific downstream elements of the Vav1/Rac1 route, contributes to the negative regulation of T-cell responses., a VAV1-Rac1-PAK1 signaling axis in mononuclear phagocytes regulating superoxide production in a stimulus-dependent manner., Rac1 has a critical role in colorectal tumor progression, The Ang II/Rac1/STAT3 pathway is an important signaling pathway in the atrial myocardium to mediate atrial structural remodeling, and losartan and statin may be able to reverse Ang II-induced atrial structural remodeling in atrial fibrillation., This study showed that PTPalpha is required for remodeling of focal adhesion during cell spreading via a pathway involving Rac1., role of RHO GTPases RAC1 and CDC42 in PGE(2)-mediated migratory responses of extravillous trophoblast cells, Identify chimaerins as candidates for the downmodulation of Rac1 in T-lymphocytes and, in addition, uncover a novel regulatory mechanism that mediates their activation in T-cells., Rac-1 coordinates changes in chondrocyte phenotype and function and stimulates the maturation process essential for skeletal development., TGFbeta1 stimulates CCN2 expression in human gingival fibroblasts through a RhoA-independent, Rac1/Cdc42-dependent mechanism, Protein kinase C-epsilon regulates sphingosine 1-phosphate-mediated migration of human lung endothelial cells through activation of phospholipase D2, protein kinase C-zeta, and Rac1, Novel mitogenic signaling pathway in airway smooth muscle cells leading from PDGF to Rac1 and cell cycle gene regulation., Data show that Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling., Data investigate the molecular mechanisms underlying Rac1-induced destabilization of junctions and found activation of the Rac target PAK1 is necessary for destabilization of cell-cell contacts., Mapping of the Rac1 GTPase surface that contacts the Rho GTPase binding domain of plexin-B1 by NMR confirms the plexin domain as a GTPase effector protein and regions neighboring the GTPase switch I and II regions are also involved in the interaction., reorganization of subsarcolemmal cytoskeletal actin by activation of Rac1 through alpha and betaPIXs in skeletal muscle is mediatedby affixin, The purpose of this study was to characterize the significance of Rho processes in the cellular cytoskeleton., Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2., As(2)O(3) induced phosphorylation and membrane translocation of the NADPH oxidase subunit p47(phox) and it also increased translocation of Rac1 and p67(phox)., We suggest that Rac1 plays a role in cellular migration not only limited to its known function in reorganization of the actin cytoskeleton, but also as part of the intracellular machinery that controls the redox balance., negative results suggested that variants of RAC1 gene did not influence the occurrence of non-syndromic mental retardation in Chinese children, Data show that Rac1 plays a significant role in the pathological adhesion of Schwannoma cells., Exogenous hydrogen sulfide inhibits superoxide formation, NOX-1 expression and Rac1 activity in human vascular smooth muscle cells., Phospholipase D activity regulates integrin-mediated cell spreading and migration by inducing GTP-Rac translocation to the plasma membrane, Rac1 activation specifically in membrane ruffles by the GEF FLJ00068 is sufficient for insulin induction of glucose uptake into skeletal-muscle cells., small GTPase Rac, a component of some NOXs, also interacts with and regulates the constitutively-expressed NOSs., a specific domain in Fas, topologically and functionally distinct from the death domain, which regulates neuritogenesis via recruitment of ezrin and activation of Rac1, DOCK180 regulates CI-MPR trafficking via SNX5 and this function is independent of its guanine nucleotide exchange factor activity toward Rac1, Rac1b and B-Raf(V600E) functionally cooperate to sustain colorectal cell viability and suggest they constitute an alternative survival pathway to oncogenic K-Ras., HIV-1 Env mdiated Rac-1 activatation is dependent on Galpha(q) activation., These data show, for the first time, that colorectal cells expressing alternative spliced Rac1b also depend on Rac1b signaling to sustain their survival., CCL2 stimulation of prostate cancer cells activates the small GTPase, Rac through the actin-associated protein PCNT1., Positive role of Tyr94 phosphorylation in EGF-induced Asef activation following the activation of Rac1., Rac1 regulates nitric oxide synthase type 2 (NOD2) trafficking and NOD2-dependent signal transduction in primary human monocytes and cell line THP-1., Rac regulates the interaction of fascin with active PKC., uPAR cooperates with integrin complexes containing beta(3) integrin to drive formation of the p130Cas-CrkII signaling complex and activation of Rac, resulting in a Rac-driven elongated-mesenchymal morphology, cell motility, and invasion., The DOCK180-ELMO1 interaction is mapped to the N-terminal 200 amino acids of DOCK180, and to the C-terminal 200 amino acids of ELMO1, comprising the ELMO1 PH domain., Confocal imaging of fluorescently labeled ZEBOV indicated that inhibition of PI3K, Akt, or Rac1 disrupted normal uptake of virus particles into cells and resulted in aberrant accumulation of virus into a cytosolic compartment, PEDF could improve the Advanced glycation end products-elicited insulin resistance in Hep3B cells by inhibiting JNK- and IkappaB kinase-dependent serine phosphorylation of IRS-1 via suppression of Rac-1 activation., Tiam1, a Rac1-specific guanine nucleotide exchange factor, was expressed mainly in the cytosol of AT2 cells exposed to mechanical strain compared with membrane localization in static cells., paxillin is a critical downstream effector of Rac1 that may be involved in PMA-stimulated migration presumably by modulating the integrity of focal complex formation., Positive regulation of migration and invasion by vasodilator-stimulated phosphoprotein via Rac1 pathway in human breast cancer cells., results suggest that Rac1 and the Rac1-specific activator Tiam1 are components of transcriptionally active beta-catenin/TCF complexes at Wnt-responsive promoters, and Rac1 and Tiam1 within these complexes serves to enhance target gene transcription, Rac1 is required for human endometrial stromal cell migration, the interaction of the RAGE cytoplasmic domain with Dia-1 is required to transduce extracellular environmental cues evoked by binding of RAGE ligands to their cell surface receptor, resulting in Rac-1 and Cdc42 activation and cellular migration, Study demonstrates tight interplay between Rho and Rac in determining different modes of tumor cell movement, revealing how tumor cells switch between different modes of movement., as a mediator of SF- and Src-stimulated NF-kappaB activity. Finally, the Src/Rac1/MKK3/6/p38 and Src/TAK1/NF-kappaB-inducing kinase pathways exhibited cross-talk at the level of MKK3., PAF-induced IEJ disruption and increased endothelial permeability requires the activation of a Tiam1-Rac1 signaling module, suggesting a novel therapeutic target against increased vascular permeability associated with inflammatory diseases., KAI1/CD82 decreased the metastatic phenotype of H1299 lung carcinoma cells by down-regulating Rac1 expression through the PI3K/Akt/mTOR pathway., Rac-1 promotes pulmonary artery smooth muscle cell proliferation by upregulation of plasminogen activator inhibitor-1, Data suggest that ARF6-mediated Rac1 activation is essential for glioma cell invasion via a signaling pathway that requires IQGAP1., Abnormal p120-catenin expression correlates with abnormal E-cadherin expression and specific small GTPase overexpression, which contribute to the malignancy-related to NSCLC., Rac1 is crucial to activate HIF-1 in RPE (retinal pigment epithelium) cells under hypoxia., Tyr-153 is the Lck-dependent phosphorylation residue and its phosphorylation negatively regulates membrane stabilization of beta2-chimaerin, decreasing its GAP activity to Rac, Rac1 and RhoA signaling simultaneously regulate cell invasion in 3D matrices., hMena possesses properties which help to regulate the formation of lamellipodia through the modulation of the activity of Rac1., Data show that TNFalpha and Il-1beta stimulate a transient, redox-dependent reorganization of the actin cytoskeleton into lamellipodia under the regulation of Rac1 and a neuronal NADPH oxidase as the source of ROS., These results demonstrate a role of PLD in hyperoxia-mediated IQGAP1 activation through Rac1 in tyrosine phosphorylation of Src and cortactin, as well as in p47(phox) translocation and reactive oxygen species formation in human lung endothelial cells., Phosphodiesterase 2 mediates redox-sensitive endothelial cell proliferation and angiogenesis by thrombin via Rac1 and NADPH oxidase 2., BPAG1e is required for efficient regulation of keratinocyte polarity and migration by determining the activation of Rac1., Activation of Rac1 GTPase contributes to VEGF-induced endothelial cell hyperpermeability., suggest host and viral genes triggering Rac1 or reactive oxygen species production as key determinants of Kaposi's sarcoma (KS) onset and potential KS chemopreventive or therapeutic targets, calcineurin/Rac1/class II PAKs pathway regulates cofilin dephosphorylation leading to secretion, role of RhoA and Rac1 GTPases in SDF1-induced adhesion, chemotaxis, and homing of multiple myeloma cells to the bone marrow, Results show that alphavbeta6- and alpha5beta1-integrin-dependent activation of Rac1 was mediated through Eps8., T-cadherin transcriptionally activated Rac1 and Cdc42., Repression of the small Rho GTPase Rac1 in human endothelial cellsseems to be an additional critical molecular mechanism in the regulation of VEGFR2 expression., Data indicate that decrease of cAMP and Rac 1 activity may be an important step in thrombin-mediated inflammatory barrier disruption., Src kinases and Rac1 but not phosphatidylinositol 3-kinases are essential to mediate Streptococcus pyogenes internalization into human endothelial cells., increased spontaneous apoptosis of double positive thymocytes and mature T cells in dominant negative Rac1 transgenic mice, LOX-1-MT1-MMP axis plays a crucial role in RhoA and Rac1 activation signalling pathways in ox-LDL stimulation., Data provide substantial evidence that Rac1 signaling inhibits the transcriptional repressor BCL-6 in colorectal cells and reveal a novel pathway that links Rac1 signaling to the regulation of gene transcription., that down-regulation of Rac1-GTPase contributes to the inhibition of angiotensin II-mediated superoxide release by 17beta-estradiol in monocytes., Upregulation of Tiam1 and Rac1 proteins may play a critical role in tumor progression of nasopharyngeal carcinoma, Findings highlight an important role for Rac1 in trastuzumab resistance of human breast cancer cells and identify the impaired trastuzumab-mediated endocytic down-regulation of ErbB2 as a novel mechanism of trastuzumab resistance., Rac1 and Rac2 are both required for efficient chemotaxis., overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression., Mtation of E-cadherin influences Rac1 and Rho activation in opposite directions., Results suggest that adiponectin promotes the migration activities of endothelial progenitor cells mainly through PI3-kinase/Cdc42/Rac1., ASF/SF2 and SRp20 are two antagonistic splicing factors regulating Rac1b expression in colorectal tumor cells., Ect2 and PKCiota are genetically and functionally linked in NSCLC, acting to coordinately drive tumor cell proliferation and invasion through formation of an oncogenic PKCiota-Par6alpha-Ect2 complex., Inhibition of Rac1 does not block human neutrophil response to high concentration gradient of chemoattractant peptide., VEGF leads to a Rac1-mediated generation of ROS, which, in turn, elevates the tyrosine phosphorylation of VE-cadherin and beta-catenin, ultimately regulating adherens junction integrity., the sensitivity of metastatic pancreatic cancer cells to benzyl isothiocyanate might be due to down-modulation of the proangiogenic molecule small GTPase Rac1, Rac1 and Cdc42 signaling has a role during early herpes simplex virus type 1 infection of keratinocytes, Inhibition of isoprenylcysteine carboxylmethyltransferase (Icmt) decreases activation of RhoA and Rac1, and in the absence of Icmt activity, addition of exogenous RhoA or Rac1 partially rescues directed and random migration, respectively., CCN3 increases the activity of the small GTPase Rac1, thereby revealing a pathway that links Cx43 directly to actin reorganization., phosphorylation of Rac1 at Ser-71, exemplarily induced by epidermal growth factor, reduces Clostridium difficile toxin A-induced changes in the intestinal barrier function., Internalization of DENV-2 into endothelial cells requires viral induction of dynamic filopodia regulated by Rac1 and Cdc42 cross-talk and myosin II motor activities., Findings show that JNK is necessary for oncogenic H-ras-induced, caspase-independent cell death, and that both PI3K and Rac1 activities are required for JNK activation and cell death., Rac1 activation enhances events that contribute to mesangial cell collagen expression, through a positive feedback loop involving phosphatidylinositol-3-kinase, Dysregulation of Rac1 and Arf6 function by RCC2 knockdown also abolished persistent migration along fibronectin fibers, indicating a functional role for RCC2 in directional cell movement., These results suggest that the novel gene, Kenae/CCDC125, acts as a regulator of cell motility through RhoA, Rac1 and cdc42., Rac inhibition reverses the phenotype of fibrotic fibroblasts, RhoA plays an antagonistic role to Rac1/Cdc42 in the control of mammary epithelial acinar morphogenesis., TEM5 expression during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of proliferation in endothelial cells., A positive prognostic value of immunohistologically determined Rac1 protein expression was found and Rac1 as a potential unfavorable prognosis biomarker in patients with early operable non-small cell lung cancer, is presented., Induction of PI3K activity by CD40L may stimulate activation of Rac1 and NOX2 inducing, oxidative stress and endothelial dysfunction., Data show that activation of the WAVE2 complex requires simultaneous interactions with prenylated Rac-GTP and acidic phospholipids, as well as a specific, Studies demonstrate using different phagocytic models that YopO specifically blocks Rac-dependent Fcgamma receptor internalization pathway., Asef2 activates Rac1 to modulate adhesion and actin dynamics and thereby regulate cell migration, Data shsow that specific binding of PP5 to activated Rac1 provides a direct mechanism by which PP5 can be stimulated and recruited to participate in Rac1-mediated signaling pathways., PAK-1 and its activator Rac1 are novel HIF-1 targets that may constitute a positive-feedback loop for induction of HIF-1alpha by thrombin and ROS, thus explaining elevated levels of PAK-1, Rac1, and HIF-1alpha in remodeled pulmonary vessels., Conclude that beta-NAD regulates the pulmonary endothelial cell barrier integrity via small GTPase Rac1- and MLCP- dependent signaling pathways., Rac1 and Rac2 GTPases are essential for normal bone marrow erythropoiesis, but they are dispensable for erythropoiesis in the spleen., expression of several highly significant cancer related genes require the activities of Rac1 and/or Cdc42 which may also play a critical role in cellular transformation, These observations indicate that group A streptococcus invasion triggers reactive oxygen species production through Rac1 activation and generated reactive oxygen species induced mitochondrial dysfunction leading to cellular apoptosis., These results demonstrate a chondrogenic-SMC fate decision mediated by cell shape, Rac1, and N-cadherin, and highlight the tight coupling between lineage commitment and the many changes in cell shape and cell adhesion that occur during morphogenesis., These data suggest that blockade of Rac1 signaling results in accumulation of type I collagen due to decreased collagenase activity., integration of Rac1 and Rab7 activities by Armus provides an important regulatory node for E-cadherin turnover and stability of cell-cell contacts, Our studies suggest that Rac1 --> Pak1/Pak2 --> NFkappaB is a separate pathway that contributes to the expression of COX-2 in HPV-induced papillomas, independently of the previously described Rac1 --> p38 --> COX-2 pathway., Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization, secondary mediators, and Rac1., TLR2 cooperates with MyD88, PI3K, and Rac1 in lipoteichoic acid-induced cPLA2/COX-2-dependent airway inflammatory responses, the Rac1 signaling axis is a critical determinant of apoptosis and tumorigenesis, Rac1 mutant in LNCaP cells promoted cell proliferation under androgen-depleted conditions both in vitro and in vivo., Protein complexes containing CYFIP/Sra/PIR121 coordinate Arf1 and Rac1 signalling during clathrin-AP-1-coated carrier biogenesis at the trans-golgi network., signal transfer of Crk/Dock180/Rac1 is implicated in actin cytoskeleton reorganization and thus in the cell proliferation, motility, invasion, and of human ovarian cancer cell line SKOV3., The p110alpha selectively mediates activation of the GTPase Rac1 to regulate barrier function., the Rac-GAP beta2-chimaerin is negatively regulated by protein kinase Cdelta-mediated phosphorylation, Nox5 does not appear to have an obligatory need for Rac-1 for its activation in human endothelial cells., in the presence of alphavbeta3-integrin Rac1 is not required for tumor angiogenesis, Results reveal a novel biological role for Rac1 and provide new insights into the mechanism regulating epidermal stem cells., Data show that podocalyxin overexpression in human embryonic kidney cells up-regulates Rac1 activity, which depends on a complex formed by podocalyxin, ERM-binding phosphoprotein 50, ezrin, and ARHGEF7, a Rac1 activator., Data identify CD2AP as a novel Rac1-associated adapter protein that participates in the regulation of epithelial cell-cell contact., AIRE may function as a regulator in the phagocytic clearance of apoptotic cells by promoting the expression of Rac 1., Suggest that Rac1 activity and Pak1 are involved in lymphovascular invasion and lymph node metastasis of urothelial carcinoma of the upper urinary tract , and may be prognostic markers for this disease., H. pylori induces the translocation of HSP90beta from the cytosol to the membrane and interaction of HSP90beta and Rac1, which leads to the activation of NADPH oxidase and production of ROS in gastric epithelial cells., Rac1 knockdown by RNAi interference confirmed the specificity of NSC23766 and requirement for Rac1 in the regulation of cyclin D1, survivin, and XIAP in breast cancer cells., Increased RAC1 is associated with vascular invasion and intrahepatic metastasis hepatocellular carcinoma., Rac1 activates phospholipase Cdelta1 through phospholipase Cbeta2, TSC2 has a role in controlling cell polarity and migration by regulating CDC42 and RAC1 activation, These findings demonstrate that interactions between Rac1 and the Hh pathway control the size of myofibroblastic hepatic stellate cells populations and have important implications for the pathogenesis of cirrhosis., The bFGF-FGFR1-PI3K-Rac1 pathway in the bone microenvironment may have a significant role in the invasion and metastasis of Ewing sarcoma., Hyaluronic acid and thrombin increase protein synthesis of MT1-MMP and activate mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and Rac-1 signaling pathways in homing of hematopoietic stem/progenitor cells., Data show that PED and Rac1 interact and that this interaction modulates cell migration/invasion processes in cancer cells through ERK1/2 pathway., decreasing beta1 chain causes alphavbeta3-integrin to become functionally dominant and promotes renal cell fibrogenesis via Rac1-mediated ERK activity., Results define the role of PIPKI-alpha in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration., Data represent a novel signaling of semaphorin 5A and plexin B3 in the control of cell motility by indirect inactivation of Rac1 through RhoGDIalpha., Perturbations of endosome morphology associated with Ras-induced non-apoptotic cell death are due to downstream activation of Rac1 combined with reciprocal inactivation of Arf6., Report mevalonate kinase deficiency compromized fiberoblast geranylgeranylation of RhoA and Rac1., Short-term treatment with atorvastatin 40 mg/d before CABG improves redox state in SVGs, by inhibiting vascular Rac1-mediated activation of NADPH-oxidase., Data show that Rac1 controls the plasma membrane localisation of PIP5Kbeta and thereby the localised synthesis of PtdIns(4,5)P required to induce neurite retraction., Studies indicate that molecular mechanisms underlying phyagocyytossis are starting to point to the interplay between two families of crucial proteins, TNFRSF19 overexpression in glioma cells activates Rac1 signaling in a Pyk2-dependent manner to drive glioma cell invasion and migration, Activation of Rac1 and Cdc42 correlated with stabilized barrier functions in intestinal epithelium., Erk1/2 MAPK and PI3K/Akt signalling triggers invasion through distinct downstream effectors involving mTOR/p70S6K and Rac1 activation., The follicular fluid-HDL-associated S1P promotes granulosa lutein cell migration via S1PR3 and RAC1 activation. This may represent a novel mechanism contributing to the development of the corpus luteum., EGF receptor regulates the permeability barrier development through the Rac1/JNK-dependent pathway., The authors find that HIV-1 entry into macrophages is sensitive to inhibitors of Na(+)/H(+) exchange, actin rearrangement, dynamin, Rac1, and Pak1., sCD40L enhances agonist-induced platelet activation and aggregation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway., These data indicated that the invasion and migration in Daoy cells were inhibited by deletion of Rac1., Rac1-mediated signaling plays a central role in secretion-dependent platelet aggregation in blood stimulated by a wide array of platelet agonists including atherosclerotic plaque., the ability of TatP to exploit the machinery of living cells, using HSPG signaling to activate Rac1 and alter TatP mobility and internalization., LFA-1-induced stabilization of ARE-containing mRNAs in T cells is dependent on HuR, and occurs through the Vav-1, Rac1/2, MKK3 and p38MAPK signaling cascade, thrombin activates the Rac1/PI3K/Akt pathway through formation of the Gbetagamma, Rac1, and p85alpha complex to induce IKKalpha/beta activation, NF-kappaB transactivation, and IL-8/CXCL8 expression in human lung epithelial cells., these data demonstrate that the activation of H-Ras and the downstream molecule Rac1 correlates with EGF-induced breast cancer cell invasion., Data show that knockdown of Tollip reduces CNF1-induced Rac1-dependent UPEC entry., Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration, Enterovirus 71 induces integrin beta1/EGFR-Rac1-dependent oxidative stress in SK-N-SH cells. Up-regulation of HO-1 exerts as a host cellular defense mechanism against EV71 infection in SK-N-SH cells., Myeloid-associated differentiation marker (MYADM) regulates Rac1 targeting to ordered membranes required for cell spreading and migration., Rac1 is critical for tumor initiation and metastasis of human non-small cell lung adenocarcinoma, Phosphatidylinositol 3'-kinase signaling pathway is essential for Rac1-induced hypoxia-inducible factor-1(alpha) and vascular endothelial growth factor expression in hypoxia., genetic polymorphism of the Rho-GTPase Rac1 is associated with azathioprine response in Inflammatory Bowel Diseases., Results suggest that calmodulin regulates the activation of Rac1 in CHRF-288-11 cells in a manner similar to that in the human platelets., A model of localised Rac1 activation in endothelial cells due to fluid flow., data suggest that activation of PKG signaling in pericytes inhibits focal adhesion formation by inhibiting Rac1, pathological mutations in LRRK2 attenuates activation of Rac1, causing disassembly of actin filaments, leading to neurite retraction., in microvascular endothelium, Rac1-mediated alterations in contact zone architecture contribute to cAMP-induced barrier stabilization., Rac1 to inhibit intracellular superoxide production as well as overcome Bcl-2-mediated drug resistance in human leukemia cells and cervical cancer cells., Results demonstrate that miR-142-3p directly and negatively regulates RAC1 in HCC cells, which highlights the importance of miRNAs in tumorigenesis., Rac1 and NOX1 are required for Rhinovirus-induced disruption of barrier function in polarized airway epithelial cells., Rac1 may be important in activation of NOX5-S in Barrett's esphageal adenocarcinoma cells., conclude that Rac1 and Hsp83 are required for the proper localization of Mys after parasitization, The authors demonstrate that the Streptococcus pyogenes FbaB is essential and sufficient to trigger endothelial cell invasion via a Rac1-dependent phagocytosis-like uptake., Tbeta(4) increases migration of colon cancer cells via activating Rac1 by elevating IQGAP1/ILK complexes, Tannerella forsythia epithelial cell entry is dependent on host PI3K signalling, purified BspA protein causes activation of this lipid kinase, and also requires the cooperation of host Rac1 GTPase., This study reveals that Rac1 is prooncogenic in that it can alter TGF-beta signalling at the R-Smad level from a tumour-suppressive towards a tumour-promoting outcome., study shows that MT1-MMP mediates the RhoA/Ca(2+) and Rac1/NADPH oxidase-dependent signaling pathways in thrombin-induced vascular responses, in motile cells Col XVII recruits BPAG1e to alpha6beta4 integrin and is necessary for activation of signaling pathways, motile behavior, and lamellipodial stability., CD81 is required for the formation of actin membrane protrusions via Rac1 activation in adhesion-dependent immune cell migration., Our study indicates that RAC1 rs10951982 risk allele increases the susceptibility to the development of colonic inflammatory bowel disease., 50% of Rac1-deficient transgenic GABAergic interneurons originating in the median ganglionic eminence fail to migrate toward the cortex due to an intrinsic defect, resulting in their inability to transition through the cell cycle G1 phase., Data identify the BAR-domain protein PACSIN2 as a Rac1 interactor that regulates Rac1-mediated cell spreading and migration., These results indicate that the small GTPase Rac1 is involved in the maintenance of stemness and malignancies in glioma stem-like cells., Data show that Semaphorin 5A (Sema5A) and plexin-B3 inhibit glioma cell invasion through Rac1 inactivation., Data indicate taht candidate genes ACTB, BZW, OCM, MACC1, NXPH1, PRPS1L1, RAC1 and RPA3, which lie within the DFNB90 region, were sequenced and no potentially causal variants were identified., The PI3K-Rac1/RhoA signaling pathway plays a vital role in IL-8 induced endothelial cell migration, The inhibitory effect of EHD2 overexpression is partially rescued by co-expression of Rac1 as measured using a protein trafficking assay., S6K1 and mTOR regulate Rac1-driven platelet activation and aggregation., Rac1 protein may control the migration of epidermal stem cells by regulating adhesion, spreading, and chemotaxis. It plays an active role in wound healing accelerated by ESC., Rac1 is an important regulator of VEGF-mediated angiogenesis and its knockdown represent an attractive approach to inhibit tumor angiogenesis and growth., Intermedin reduces HUVEC permeability via Rac1-mediated actin cytoskeleton rearrangement., a Rac1/PAK1 cascade controls beta-catenin S675 phosphorylation and full activation in colon cancer cells, p66Shc activation by mutSOD1 causes a strong decrease in the activity of the small GTPase Rac1 through a redox-sensitive regulation., Arf GTPases may be central components in WAVE signalling, acting directly, alongside Rac1., Tiam1 and Rac1 expressions may be independent predictors for the poor prognosis in patients with primary gallbladder carcinoma, Involvement of 14-3-3 proteins in the second epidermal growth factor-induced wave of Rac1 activation in the process of cell migration., Coronin 1A promotes a cytoskeletal-based feedback loop that facilitates Rac1 translocation and activation, Angiopoietin-1 requires IQ domain GTPase-activating protein 1 to activate Rac1 and promote endothelial barrier defense., Data show that Rac1 was highly activated in PTEN deficient and IGF-IR overexpressing Trastuzumab-resistant cells in a HER2-independent manner., AexU effector protein of Aeromonas veronii is a novel type three secretion system effector which specifically inactivates Rac1 to disrupt actin cytoskeleton and has an alternative cytotoxic pathway through beta4-integrin mediation., The mRNA and protein levels of Rac1 and Rac2 are elevated following exposure of endothelial progenitor cells to the chemokine SDF-1alpha., Study demonstrated that hypoxia-induced HIF-1alpha expression involves a cascade of signaling events including ROS generation, activation of PI3K and ERK signaling, and subsequent activation of Rac1., Burkholderia cenocepacia perturbs actin architecture by inactivating Rho family GTPases, particularly Rac1 and Cdc42., The RNAi-mediated depletion of HACE1 blocks the ubiquitylation of active Rac1 and increases GTP-bound Rac1 cellular levels., signaling from integrin alpha6beta4 facilitates lysophosphatidic acid- stimulated chemotaxis through preferential activation of RhoA, which, in turn, facilitates activation of Rac1, Rac1b was required for NT3-stimulated cell proliferation of marrow isolated adult multilineage inducible cells toward an early neuronal phenotype., PDGFRalpha signaling in glioblastomas leads to Src-dependent phosphorylation of the guanine nucleotide exchange factor Dock180 at tyrosine 1811 (Dock180(Y1811)) that results in activation of the GTPase Rac1 and subsequent cell growth and invasion., No immunostaining to Rac1 was observed in the ameloblastomas studied., Data suggest that an anti-Wnt5a antibody was capable of suppressing Wnt5a-dependent internalization of Fz2 receptor, resulting in the prevention of metastasis of gastric cancer cells by inhibiting the activation of Rac1 and the expression of laminin gamma2., Rac1 is constitutively expressed at high levels throughout the airway of recurrent respiratory papillomatosis patients, independent of active HPV infection, and is a targetable host-susceptibility factor, Sonic Hedgehog activates the GTPases Rac1 and RhoA in a Gli-independent manner through coupling of smoothened to Gi proteins., IFNgamma induces a higher basal level of F-actin and activation of Rac1, affecting the response to stimuli that induce cytoskeleton rearrangement such as phagocytic or chemotactic stimuli., data suggest that Rac1b expression acts as a modulator or transducer of various signaling pathways that lead to neurofibrillary tangle formation and membrane dysfunction in a subgroup of CBF NB neurons in AD., examined integrin beta(1) , ECAD and rac1 expression in SCLC and analyzed the prognostic value of these markers, Overexpression of p38beta or Rac1 significantly enhanced (1.9- and 3.9-fold, respectively), the tRA-stimulated NIS expression in MCF-7 cells., mitochondrial import and direct electron transfer from cytochrome c to Rac1 modulates mitochondrial H(2)O(2) production in alveolar macrophages pulmonary fibrosis., Aberrant methylation of PSD occurs in UC-associated colorectal mucosa, enabling circumvention of Rac1 immune responses governing neutrophil chemotaxis and apoptosis, and plays a pivotal role in the mechanisms underlying UC-associated carcinogenesis., delta-catenin facilitated invasion of lung cancer cells by upregulating the mRNA and protein levels of Rac1, Rac1 positively regulates CXCR4 function and identifies the Rac1-CXCR4 axis as a new target for preventing HIV-1 infection., GEF Trio is responsible for lamellipodia formation through its N-terminal DH-PH domain in a Rac1-dependent manner during fibronectin-mediated spreading and migration., C. pneumoniae infection of mononuclear cells stimulates IL-1beta production dependent on a NLRP3 inflammasome-mediated processing of proIL-1beta which is controlled by Rac1., results indicate that VEGF serves a positive regulatory role via its interaction with VEGF R1 to activate Rac1 and enhance alveolar macrophage apoptotic cell clearance, a new role for Rac1 in cell signaling, showing that this GTPase triggers T-cell proliferation upon IL-2 stimulation by associating with PYGM and modulating its enzymatic activity., Compared with that of adjacent non-cancerous gastric mucosa, the expression of Rac1 in gastric carcinoma tissues was significantly increased., vitreous-transformed human retinal pigment epithelial cells undergo cytoskeletal rearrangements via Rac1 GTPase-dependent pathways that modulate LIMK1 and cofilin activity., Non-small cell lung carcinoma cell motility, rac activation and metastatic dissemination are mediated by protein kinase C epsilon, Beclin 1 coordinates actin dynamics and membrane phospholipid synthesis to promote efficient apoptotic cell engulfment with Rac1, Twist1 cooperates with BMI1 to suppress let-7i expression, which results in upregulation of NEDD9 and DOCK3, leading to RAC1 activation and enabling mesenchymal-mode movement in three-dimensional environments., Data show that NADPH oxidase in monocytes was highly activated by enhancing Rac1 expression in Chinese overweight adolescents and Rac1 may act as a link between obesity and oxidative stress., Rac1b promotes K-ras-induced lung tumorigenesis., we found that merlin regulated expression of SEMA3F through Rho GTPase family member Rac1, Data reveal a novel Rac1-dependent signalling pathway that, through Nedd4-mediated ubiquitylation of Dvl1, stimulates the maturation of epithelial cell-cell contacts., Radixin plays an important role in promoting cell migration by regulating Rac1-mediated epithelial polarity and formation of adherens junctions through Vav GEFs., Phospho-mimetic S31E-RhoGDI2 exhibits reduced binding to Rac1 relative to wild type, with a concomitant failure to reduce levels of activated endogenous Rac1 or remove Rac1 from membranes., Data show that Mtss1 drives enhanced junction formation specifically by elevating Rac-GTP., Rac1 plays an essential role in the activation of radiation-induced ERK1/2 signaling and subsequent G2/M checkpoint response and promotes cell survival after irradiation treatment., BDNF knockdown inhibited cell invasion probably through the blocked actin polymerization and the correlated inactivation of RhoA or Rac1., HACE1 as an antagonist of cell migration through its ability to degrade active Rac1., These findings demonstrate for the first time that Cryptococcus neoformans Plb1 aids fungal traversal across the blood-brain barrier by activating host cell Rac1 and its association with STAT3., LRFN4 complexed with 14-3-3s and NCK1 to mediate elongation in monocytic cells via Rac-1-mediated actin cytoskeleton reorganization, Host cell kinases, alpha5 and beta1 integrins, and Rac1 signalling on the microtubule cytoskeleton are important for non-typable Haemophilus influenzae invasion of respiratory epithelial cells., a critical role for H(2)O(2) in angiotensin-II signaling to the endothelial cytoskeleton in a novel pathway that is critically dependent on MARCKS, Rac1, and c-Abl., IL-8-Rac1/RhoA-p38MAPK signaling pathway plays a vital role in the IL-8-induced endothelial cell migration., Rac1 modulates the SDF-1-induced migration and invasion of glioma cells., Stat3 forms a multiprotein complex with Rac1 and PKC in an hypoxia-reoxygenation-dependent manner., overexpression of Dsg3 results in a remarkable increase of Rac1 and Cdc42 activities, 14-3-3zeta enhances prostate cancer cell-matrix interactions, motility and transendothelial migration in vitro via activation of Rac1-GTPase and is an important target for therapeutic interventions for prostate cancer., Recurrent somatic RAC1 mutations in melanoma., CD151 links alpha(3)beta(1)/alpha(6)beta(1) integrins to Ras, Rac1, and Cdc42 by promoting the formation of multimolecular complexes in the membrane, which leads to the up-regulation of adhesion-dependent small GTPase activation, PI3K, Rac1 and PAK1 may play important roles in the pathogenesis of EMPD., automated image analysis of MT assembly dynamics identified MARK2 as a target regulated downstream of Rac1 that promotes oriented MT growth in the leading edge to mediate directed cell migration., Glycogen synthase kinase 3beta inhibition prevents monocyte migration across brain endothelial cells via Rac1-GTPase suppression and down-regulation of active integrin conformation., Characterization and functional analysis of the calmodulin-binding domain of Rac1 GTPase, MKlp1-CYK4 centralspindlin complex is a guanosine triphosphatase-activating protein (GAP) for Rac1 and not RhoA., Upregulation of Rac1 activity by Wnt3a temporally correlated with enhanced p120-catenin binding to Rac1 and Vav2., results validate the WNK2 gene as a recurrent target for epigenetic silencing in glia-derived brain tumours and provide first mechanistic evidence for a tumour-suppressing role of WNK2 that is related to Rac1 signalling and tumour cell invasion and growth, Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration., Loss of dorsal stress fibers either by depleting alpha-actinin-1 or Rac1 results in a beta-actin accumulation at the leading edge in migrating and spreading cells., Neuregulin mediates F-actin-driven cell migration through inhibition of protein kinase D1 via Rac1 protein, Rac1 activation causes relocalization of Net1 isoforms outside the nucleus and stimulates Net1A catalytic activity., Rac can serve as a starting point in defining cell polarity., PI3K-C2alpha plays the crucial role in S1P(1) internalization into the intracellular vesicular compartment, Rac1 activation on endosomes, and thereby migration through regulating vesicular trafficking in ECs, RhoGAP, BGIN-polubuiquitin interactions enhance BGIN membrane distribution and relay poly-Ub signals to enact Rac1 inactivation., The data suggest that CD133+ GBM cells highly express Rac1 and have greater potential to migrate and invade through activated Rac1-GTP., Interaction of Rac1 with the C-terminal cytoplasmic domain of CD81 is a novel regulatory mechanism of the GTPase activity turnover., These data show that Rac1 is activated during muscle contraction in murine and human skeletal muscle and suggest that Rac1 and possibly the actin cytoskeleton are novel regulators of contraction-stimulated glucose uptake., The activated melanoma RAC1(P29S) protein maintains intrinsic GTP hydrolysis and is spontaneously activated by substantially increased inherent GDP/GTP nucleotide exchange., Coronin-1C overexpression is associated withand hepatocellular carcinoma growth through enhancement of tumor cell proliferation and migration, which are correlated with Rac-1 activation., ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology, The Rho-family small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), has been implicated in renal and cardiac disease., Positive rates of Rac1, Pak1 and Rock1 expression in normal tissue, dysplasia and gastric carcinoma show an increasing trend and are correlated with tumor lymph node metastasis and TNM stage., Upregulation of rac1 is associated with metastatic, castration-resistant prostate tumors., PGD(2)-DP signaling reduces vascular permeability via endothelial cAMP/PKA/Tiam1/Rac1 pathway., these results suggest that the progression of pancreatic tumors is partially controlled by the balance between Tiam1-rac1 and RhoA., we characterized Rac1 as a direct target of miR-124, Our data suggest that Rac contributes to the progression of melanoma and that Tiam1 may activate Rac in nodular presentations., The constitutively-active Rac1 mutant exhibited temporary and all-time immobilizations in the FA zone, suggesting that upon PIX-induced Rac1 activation at the FA-protein islands, Rac1 tends to be immobilized at the FA-protein islands., study identified several missense mutations for RAC1 and RAC2, with some of the mutant proteins, including RAC1(P29S), RAC1(C157Y), RAC2(P29L), and RAC2(P29Q), being found to be activated and transforming; activating mutations of RAC GTPases were thus found in a wide variety of cancers at a low frequency, The findings show that Rac1 is a regulator of insulin-stimulated glucose uptake and a novel candidate involved in skeletal muscle insulin resistance., RAC1 could play a critical role in the neuropathological events associated with autism. Review., Cell migration experiments point towards the inhibition of p66Shc-rac1-mediated migration in the presence of ascorbic acid. Finally, results are suggestive that ascorbic acid-mediated decrease in Shc expression, Rac1 activation was not affected by Jak2 or Stat3 RNA interference., Results document the expression of RAC1b in normal thyroid cells as well as overexpression in a subset of PTCs. They suggest a possible interplay between BRAF V600E and RAC1b contributing to poor clinical outcome., Rac1, HIF-1alpha, and VEGF play an important role in tumor invasion and metastasis, especially in tumor angiogenesis., study provides evidence the large GTPase Dyn2 regulates the small GTPase Rac1 to potentiate invasive migration of pancreatic tumor cells; Dyn2 plays an essential role in regulating Rac1-mediated pancreatic tumor cell migration through modulation of the Rac1 activator Vav1 via a direct interaction, Downregulation of RAC1 sensitizes colon cancer cells to dihydroartemisinin-induced cell cycle arrest and apoptosis., Rac1 differentially modulate cigarette smoke-induced airway cell migration through p120-catenin-dependent and -independent pathways, Rac1 is inhibited during starvation-induced autophagy in keratinocytes., We conclude that NDV treatment induced EGAS viability suppression, but subsequent downregulation of Rac1 gene may reduce the NDV replication and lead to regrowth of EGAS tissue., findings indicate that a chemokine-controlled pathway, consisting of Galphai2, ELMO1/Dock180, Rac1 and Rac2, regulates the actin cytoskeleton during breast cancer metastasis, Data indicate that Rnd1 efficiently displaces Rac1 from its complex with Plexin-B1 but not vice versa., Data indicate CCN1 can induce actin reorganization, formation of lamellipodia, and cell migration/invasion through the alphaV integrins/Rac1/ERK signaling axis; these CCN1-dependent activities can be effectively suppressed by monoclonal antibody YM1B., Abrogation of Rac1 signaling causes DNA double-strand breaks in acute monocytic leukemia cells harbouring the MLL-AF9 oncogene., These results indicate that statins exert their pleiotropic effects through SmgGDS upregulation with a resultant Rac1 degradation and reduced oxidative stress in animals and humans., Sole transphosphorylation of p21-activated kinases is not sufficient to activate Erk1/2. It requires complex formation of both kinases with GTP-Rac1 to unleash cAMP-PKA-boosted activation of Raf-Mek-Erk., Single-nucleotide polymorphism in Rac1 is associated with response to therapy in Crohn's disease., Inhibition of ARF1 or Rac1 expression markedly impacts the ability of MDA-MB-231 cells to migrate upon Epidermal Growth Factor stimulation., The action of DOCK7 in vivo may involve the coordinated integration of Cdc42/Rac GTPase signaling in the context of the membrane recruitment of a DOCK7 guanine nucleotide exchange factor (GEF) complex., The Atypical guanine nucleotide exchange factor Dock4 regulates neurite differentiation through modulation of Rac1 GTPase and actin dynamics., Our results describe a novel molecular cascade that regulates redox signaling by the coordinated regulation of Rac1 and by linking components of the polarity complex to the NADPH oxidase., activated Rac1/Cdc42 is a vascular regulator of tumor angiogenesis and that it may reduce stability of the p53 protein to promote VEGF expression by enhancing p53 protein ubiquitin, Rac1 may play an important role in cervical cancer progression and could be a potential target for anticancer therapy., CNF-Y increases Yop translocation in Yersinia enterocolitica-infected cells up to 5-fold. CNF-Y strongly activated RhoA and also delayed in time Rac1 and Cdc42, Nucleophosmin1 is a negative regulator of the small GTPase Rac1., Rac regulates the collagen-induced HSP27 phosphorylation via p44/p42 MAP kinase in human platelets, resulting in the stimulation of platelet-derived growth factor-AB secretion and the release of CD40 ligand., CTGF acting through Rac1 activates the MLK3/JNK signaling pathway, which in turn initiates AP-1 activation and recruitment of c-Jun and c-Fos to the collagen I promoter and ultimately induces collagen I expression in human lung fibroblasts, we demonstrated the regulation of targeting/accumulation of the RhoGDIalpha-Rac1 complex to phagosomes, Rac1 GTPase is a key component of cardiovascular pathologies, including the endothelial dysfunction, cardiac hypertrophy and fibrosis, atrial fibrillation, stroke, hypertension, and chronic kidney disease. [Review], Immunosuppressive drug azathioprine inhibits endothelial cell rac1 activity to reduce inflammation and the progression of aortic aneurysms., FERM domain containing protein 7 interacts with the Rho GDP dissociation inhibitor and specifically activates Rac1 signaling., mechanical stimulation may attenuate NGFbeta signaling through Rac1, Data indicate mTOR kinase-independent function and mechanism of Rictor in the regulation of neutrophil chemotaxis, and suggest that the small Rho GTPases Rac and Cdc42 serve as downstream effectors of Rictor to regulate actin assembly., Data indicate that srGAP1 possesses a GAP activity specific to Rac1 and is recruited to lamellipodia in a Rac1-dependent manner., Decorin may interfere with angiogenesis by downregulating hypoxia-induced Met, Rac1, HIF-1alpha and VEGF expression in RPE cells, which suggests a potential strategy for the inhibition of CNV., High Rac-1 expression and lymph node metastasis were two independent factors for poor survival., This study concludes that Rac1 T108 is phosphorylated by ERK in response to epidermal growth factor, which plays an important role in regulating Rac1., Recent insights at the molecular and cellular levels are paving the way for a more directed and detailed approach to target mechanisms of RAC1 regulating angiogenesis and metastasis, These results provide evidence for a key role of Rac1 in a pathway that regulates IL-1-induced gene expression depending on receptor endocytosis., FlnA mutations alter the balance between RhoA and Rac1 GTPases activities in favor of RhoA., results demonstrate that miR-320a functions as a tumour-suppressive miRNA through targeting Rac1 in colorectal cancer, Human TIPE2 is an endogenous inhibitor of Rac1 in hepatocellular carcinoma (HCC) by which it attenuates invasion and metastasis of HCC., Data reveal that NEDD9 can regulate 3D migration speed independent of the Rac1 morphology switch., Invasion of host cells, which occurs at a low frequency, does not seem linked to Rac1 activation by Vibrio parahaemolyticus VopC, but instead appears to require CDC42., Authors propose a model for Rac1 activation where SIRT1/2 positively modulates the DVL/TIAM1/Rac1 axis and promotes sustained pathway activation., Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5).extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1., Rac1 inhibition mitigated the oxidative/nitrosative stress, prevented calcium-dependent ER-stress, and partially rescued UPS function, These data highlight a novel MT1-MMP/MMP2/RAC1 signaling axis in melanoma., These results indicated that Rac1 mediated shear stress-induced endothelial cells migration, the SNTA1/P66shc-mediated Rac1 activation resulted in an increase in reactive oxygen species (ROS) production and migratory potential in human breast cancer cells., SNPs in the RAC1 gene are associated with some clinical and biochemical parameters related to the development and progression of hypertension., Rac1 contribute to chronic lymphocytic leukemia cells proliferation and chemoresistance., FilGAP may function as a mediator of the regulation of Rac by Arf6., TIAM1-RAC1-NOX2 signalling axis is activated in the initial stages of diabetes to increase intracellular ROS leading to mitochondrial damage and accelerated capillary cell apoptosis, RhoGDI2 inhibits trophoblast cell migration, and this function may involve suppression of RAC1 activation., HIV-1 activates cytoskeletal proteins during monocyte-endothelial interactions and increase transcription and activation of Rac1 in brain tissues, while CCR5 antagonists prevented these HIV-1-induced alterations., data outline a synergistic action of nectin-1 and -4 in the early steps of AJ formation and implicate this interaction in modulating the Rac1 signaling pathway, Rab5C modulates Rac1-mediated cell motility., These results suggest a new model in which caveolin-1 might be involved in Salmonella entry via its interaction with SopE and Rac1, leading to enhanced membrane ruffling for phagocytosis into host cells., data show that bile acids are key in the breakdown of the blood-brain barrier during cholestatic liver disease, and that these permeabilizing effects were due to the activation of Rac1 and downstream phosphorylation of the tight junction protein occludin., Our study did not show any associationbetween the assessed RAC1 SNPs and CD in Iranian patients, Study demonstrates that increased DGKzeta protein levels in SW620 cells are associated with increased Rho GTPase activity and downstream signaling; silencing of DGKzeta expression in SW620 cells decreased Rac1 and RhoA activity and attenuated cell invasion; DGKzeta silencing also attenuated the invasiveness of PC-3 prostate cancer and MDA-MB-231 breast cancer cells., The M3 receptor facilitates interaction of the VE-cadherin-based adherens junctional complex and the actin-based cytoskeleton by maintaining Rac1 activity, which regulates the interaction between IQGAP1/Rac1 and IQGAP1/beta-catenin., we demonstrate that innate immune functions of macrophages ensue at least partly through a homeostatic Wnt5a-Fz5-NF-kappaB (p65) circuit, which is Rac1 dependent., RAC1 is an important downstream molecule of EGF-EGFR signaling involved in non-small-cell lung cancer cell migration., Our results demonstrate a new mechanism of modulation of RAC1 inflammatory pathway through a cross-talk between NF-kappaB and NRF2., Suppression of p21Rac activity assists innate immunity in bactericidal activity and may induce remission in inflammatory bowel disease., Higher levels of RAC1 expression are found in head and neck squamous cell carcinoma patient tumors with poor early or late responses to chemo-radiotherapy., High RAC1 activity is associated with serous ovarian cancer., RAC1b overexpression constitutes a marker of poor prognosis in KRAS/BRAF WT mCRC patients treated with first-line FOLFOX/XELOX therapy., Rac1 activation is dependent on c-met activity on the perinuclear endosome., Data suggest PIKFYVE (phosphoinositide kinase FYVE), MTMR3 (myotubularin related protein 3), and their product phosphatidylinositol 5-phosphate) are involved in activation of RAC1; this process regulates of migration/invasion of carcinoma/sarcoma., Inhibition of PAK activation at late G2-phase centrosomes caused by Rac1 inactivation coincides with impeded activation of Aurora A and the CyclinB/Cdk1 complex and delayed mitotic entry., MiR-200b suppresses arsenic-transformed cell migration by targeting PKCalpha and Wnt5b-PKCalpha positive feedback loop and inhibiting Rac1 activation., Rac1-induced lamellipodial motility consists of two distinct activities, PI3K-dependent outward extension and PI3K-independent ruffling, MMP3, known to be expressed in PDA, was found to be associated with expression of Rac1b, a tumorigenic splice isoform of Rac1, in all stages of pancreatic cancer., Authors propose a model whereby vimentin promotes FAK stabilization through VAV2-mediated Rac1 activation. This model may explain why vimentin expressing metastatic lung cancer cells are more motile and invasive., Describe here an invadopodia disassembly model, where a signalling axis involving TrioGEF, Rac1, Pak1, and phosphorylation of cortactin, causes invadopodia dissolution., TIAM1 is activated by phosphatidylinositol 5-phosphate which activates RAC1, regulating actin dynamics and cell invasion., SDF-1alpha stimulates the CXCR4/PI3K/Rac1 signaling pathway and actin cytoskeleton rearrangement to suppress endothelial permeability., the present study characterized a novel Nck-1-ELMO1 interaction and defined a new role for Nck-1 in regulating Rac1 activity., These findings show that overexpression of PODXL enhanced invadopodia formation and tumor metastasis by inducing Rac1/Cdc42/cortactin signaling network., Rac1 is a novel, direct target of miR-124., Results indicate that Coronin1 proteins are at the center of a regulatory hub that coordinates Rac1 activation, effector exchange, and the F-actin organization state during cell signaling., By inducing and activating Rap1 and Rac1., A Rac1-Aurora A-MCAK signaling pathway mediates endothelial cell polarization and directional migration by promoting regional differences in microtubule dynamics., The DDX3-Rac1-beta-catenin regulatory axis in modulating the expression of Wnt/beta-catenin target genes., TIPE1 induced apoptosis in HCC cells by negatively regulating Rac1 pathway, MTOR regulate EMT at least in part by down regulation of RhoA and Rac1 signaling pathways., The clinical and pathological associations of RAC1(P29S) in a cohort of 814 primary cutaneous melanomas with known BRAF and NRAS mutation status, were investigated., Melanoma cell lines possessing the RAC1 hotspot variant., Manipulation of Rac1 expression selectively affects the expression pattern within the galectin network at the level of proteins and distinct aspects of cell surface glycosylation., Data indicate that arachidonic acid induces the direct interaction of Rac-GTP-bound p67(phox) with the C-terminal cytosolic region of phagocyte NADPH oxidase Nox2., Dietary folate affects metastasis through the regulation of the carboxyl methylation of Rho family GTPases RhoA and Rac1., proliferation was linked to a novel DEPDC1B-Rac1-ERK1/2 signaling axis in oral cancer cell lines., Inactivation of RhoA due to lack of prenylation leads to Rac1 activation and subsequent priming for IL-1beta secretion., Rac1 has a role in mediating SOX9 expression in inner meniscus cells, AngII/Rac1/STAT3 signaling as a mechanism for atrial structural remodeling, Rac1 protein was overexpressed in human colorectal cancer cells., A sequence variant in human KALRN impairs protein ability to activate Rac1 and coincides with reduced cortical thickness., results suggest that Rac1 oxidation at Cys(18) is a novel posttranslational modification that upregulates Rac1 activity, The review highlights the multiple interacting pathways involved in Rac1 activation in cardiovascular and cerebrovascular diseases as well as in in platelet activation., metformin impairs Rho GTPases signaling to induce apoptosis via JNK pathway, these results indicate that activation of a RASAL2/ARHGAP24/RAC1 module contributes to TNBC tumorigenesis and identify a context-dependent role of RASAL2 in breast cancer., cIAP2 is in conclusion a regulator of human intestinal wound healing through enhanced migration along with activation of Rac1, LRRK2 and clathrin-light chains co-localize on endosomes and inhibit Rac1 activity., It regulates actin polymerization to form lamellipodia, which is a critical event for cell migration of prostate cancer., CD147 has a role in promoting Src-dependent activation of Rac1 signaling through STAT3/DOCK8 during the motility of hepatocellular carcinoma cells, Higher expression of RAC1 and genes related to the mineralocorticoid pathway was identified in Chilean subjects with a high-salt intake, suggesting that RAC1 could represent a mediator of Cardiovascular damage induced by sodium., Glioma stem cells preferentially secrete Sema3C and coordinately express PlexinA2/D1 receptors to activate Rac1/nuclear factor (NF)-kB signaling., The androgen-triggered AR/filamin A complex controls, through Rac 1, the decision of cells to halt cell cycle and migration., RAGE/MT1-MMP axis modified HMBG-1-mediated TF expression through RhoA and Rac1 activation and NF-kappaB phosphorylation in endothelial cells, Inhibition of GSK3beta attenuated the migration and invasion of glioblastoma cells associated with suppression focal adhesion kinase, guanine nucleotide exchange factors/Rac1 and c-Jun N-terminal kinase., Our findings demonstrate the ability of SEMA3F to inhibit the stemness of human CRC cells by suppressing Rac1 activation, which suggests a novel therapeutic approach for colorectal cancer, Whereas most nonmuscle myosin IIA (MIIA) at the leading edge assembled into dorsal contractile arcs, a substantial subset assembled in or was captured within maturing focal adhesions, and this behavior was promoted by active Rac1., Suggest a new model of VE-cadherin adhesive interaction mediated by Rac1-induced reduction of mechanical tension at endothelial cell adherens junctions, resulting in the stabilization of VE-cadherin adhesions., These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be involved in the rearrangement of cytoskeleton in lung cancer cells., The present study showed that rac1 overexpression is associated with cell epithelial-mesenchymal transition and poor epithelial ovarian cancer prognosis, Given its pivotal role in gastric tumorigenesis and progression, Rac1 can serve as a promising therapeutic target for gastric cancer., protective effect of Elmo1 and Dock180 is mediated by activation of Rac1, p21-activated kinase (PAK) and AKT/protein kinase B (AKT) signaling, Nuclear Rac1 shuttling is a finely tuned mechanism for controlling nuclear shape and organization and cell invasiveness, supports a critical role for HACE1 in breast cancer progression and identifies patients that may benefit from Rac-targeted therapies., CUL3 regulates TIAM1 abundance and subsequent RAC1 signaling., Results supported that miR-512-3p could inhibit tumor cell adhesion, migration, and invasion by regulating the RAC1 activity via DOCK3 in NSCLC A549 and H1299 cell lines., biological significance of this PKCtheta;/alphaPIX/Rac 1 GTPase/PYGM signaling pathway seems to be the control of different cellular responses such as migration and proliferation, Study identifies a bidirectional (phosphorylation and dephosphorylation) regulatory mechanism controlling Tiam1 stability and provides new insights on how EGFR signaling triggers Rac1 activation and cancer development., accumulation. These data suggest that Rac1 GTPase plays an important role in signaling and contributes to the sensitivity of cervical cancer cells under UV or gamma radiation treatments., Kaempferol-3-O-rutinoside induces the activation of RhoA and Rac1, downstream effectors of the FAK signaling pathway., a role for ARF6 in linking EGF-receptor signaling to Rac1 recruitment and activation at the plasma membrane to promote breast cancer cell directed migration, Coro1C mediated Rac1 trafficking through actin-rich vesicles., In this review, we summarize the current understanding of GEFs and GAPs for Rac1, with emphasis on the molecular function and disease implication of these regulators in the nervous system., genetic association study in population of children/adolescents in Israel, Rap1- and Rac1-GTPase activation have roles in hypoxia/reoxygenation-experienced cancer cell migration and metastasis via the expression of thymosin beta-4, ELMO1 is expressed in rheumatoid arthritis synovium, promotes cell migration and invasion, and regulates Rac1 activity, thereby mediating rheumatoid arthritis pathogenicity., OCRL inhibits Rac1 activation in osteoarthritis development., within the same cell type, EGFR and DOCK180 regulate Rac1 activation by newly-formed contacts, but control separate cellular events that cooperate to stabilise junctions., Rac1-induced actin assembly and subsequent AJ formation critically depends on FMNL2., Induction of ezrin activation by Rac1 signaling triggers a conformational change in NHERF1, which is then able to bind and stabilize misfolded CFTR at the plasma membrane., Rich1 negatively regulates the epithelial cell cycle, proliferation and adhesion by CDC42/RAC1-PAK1-Erk1/2 pathway., Ketorolac has a novel pharmacologic activity conferred by the R-enantiomer and R-ketorolac achieves sufficient levels in the peritoneal cavity to inhibit Rac1 and Cdc42, contributing to the observed survival benefit in women who received ketorolac, The P-Rex1-Rac1 interface is critical for Rac1 activation in breast cancer cells., our data show the importance of spatio-temporal regulation of the actin cytoskeleton through Trio and Rac1 at VE-cadherin-based cell-cell junctions in the maintenance of the endothelial barrier., Expression of RhoA and Rac1 was absent in fibroblasts of adjacent normal tissue and in compromised lymph nodes. Based on our findings that no significant changes were observed between primary and metastatic lymph nodes, RAC1 P29S has a role in regulating PD-L1 expression in melanoma, RalA activation was remarkably impaired in rac1-deficient skeletal muscle fibres., Src-mediated Y724 phosphorylation in ELMO1 plays a critical role for cell spreading via activation of Rac1, leading to promotion of cell migration., The TNF-alpha could suppress the osteogenic differentiation of dental pulp stem cells via increasing the expression of RAC1, which could activate the Wnt/beta-catenin signaling pathway and liberate beta-catenin to translocate into the nucleus., Data show that polyclonal antibody (pAb) of Ras-related C3 botulinum toxin substrate 1 (Rac1) protein was successfully prepared, which could specifically recognize Rac1 protein in several natural samples., Rac1 and related cell motility pathways might be associated with plasma adiponectin levels and biological functions of adiponectin., RAC1, the human ortholog of mouse Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization., WNT10B enhances proliferation through beta-catenin and RAC1 GTPase in human corneal endothelial cells., second messengers activate the Rac1 signal, which sets in motion a cascade whereby PAKs phosphorylate and negatively regulate PREX2 to decrease Rac1 activation., MARCKS upregulation increases vascular smooth muscle cell motility by activation of Rac1 and Cdc42, promoting neointima formation., Gnb isoforms control a signaling pathway comprising Rac1, Plcbeta2, and Plcbeta3 leading to LFA-1 activation and neutrophil arrest in vivo, Rac1 is involved in HMGB1induced hyperpermeability in pulmonary microvascular endothelial cells via MAPK signal transduction., Data indicate enantiomer selective interaction of R-naproxen and R-ketorolac with Rho family GTPases Rac1 and Cdc42., RAC1 overexpression promoted the proliferation of lens epithelial cells. RAC1 overexpression also promoted migration and invasion of lens epithelial cells and had an influence on the epithelial-mesenchymal transition process., we discovered distinct predictive performance of Rac1 and Cdc42 depending on the migration modes, indicating that Rac1 and Cdc42 contribute to persistent and random migration, respectively, Rab23 enhance squamous cell carcinoma cell invasion via up-regulating Rac1., Data suggest LPA (lysophosphatidic acid; acting via LPAR1) and endothelin activate Cdc42, concurrent with biphasic decrease in Rac1 activity, differential effects on RhoA; LPA/endothelin stim. leads to remodeling of invadosomes in melanoma cells., inhibition of FAK phosphorylation at Y397 or Rac1 activity can serve as a therapeutic strategy for treating patients with metastatic oral squamous cell carcinoma, This study suggested that polymorphisms of RAC1 gene might influence the susceptibility to end-stage renal disease in Chinese Han population., RAC1/RAC2 and SFK are proximal and essential for phosphatidylinositol 3-kinase (PI3K) activation in NK cell-mediated direct cytotoxicity against Cryptococcus neoformans., Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator.,
SP_COMMENT domain:The effector region mediates interaction with DEF6., enzyme regulation:Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase., function:Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction., function:Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles., similarity:Belongs to the small GTPase superfamily. Rho family., subcellular location:Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine (By similarity). Identified by mass spectrometry in melanosome fractions from stage I to stage IV., subunit:Interacts with the GEF proteins PREX1, RASGRF2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-dependent manner. Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. Interacts with RALBP1 via its effector domain. Interacts with PLXNB1. Part of a complex with MAP2K3, MAP3K3, CCM2 and DEF6. Interacts with BAIAP2, BAIAP2L1, CYFIP1/SRA-1 and DEF6. Interacts with Y.pseudotuberculosis YPKA and PLCB2. Interacts with NOXA1. Interacts with ARHGEF2. Interacts with NISCH., tissue specificity:Isoform B is predominantly identified in skin and epithelial tissues from the intestinal tract. The expression of isoform B is elevated in colorectal tumors at various stages of neoplastic progression, as compared to their respective adjacent tissues.,
ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)(RAC2) ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)(RAC2) Related Genes Homo sapiens
CHROMOSOME 22,
CYTOBAND 22q13.1,
ENSEMBL_GENE_ID ENSG00000128340,
GENERIF_SUMMARY Interaction between p21-activated protein kinase and Rac during differentiation of HL-60 human promyelocytic leukemia cell, Rac2 is activated via a T cell receptor/DOCK2 signal transduction pathway that activates IL-2 transcription in Jurkat cells, dissociations of Rac1 and Rac2 from LyGDI enable the PI 3-kinase-dependent translocations of Rac GTPases to the plasma membrane, Rac2 does not have the same role as Rac1 in the human NADPH oxidase complex, in neutrophils, Rac2 and Cdc42 are involved in FcR- and CR3-induced activation and for properly functioning signal transduction involved in the generation of oxygen radicals., Our results showed a low frequency of mutation and no hot spots of mutation in Rac2 gene in brain tumors, suggesting a decreased possibility of Rac2 in the brain tumorigenesis., diminished rho family, small GTP-binding protein Rac2(Rac2) expression in cord blood neutrophils may contribute to the defects observed in cord blood neutrophil function, Rac1 and Rac2 have distinct roles in regulating cell morphology, migration and invasion, but are not essential for macrophage migration or chemotaxis., Endogenous P-Rex1 translocates to areas of Rac2 and cytoskeletal activation at the leading edge in response to chemoattractant stimuli in human neutrophils and that this translocation can be negatively modulated by activation of PKA and by cell adhesion., RACK1 amd Rac2 are components of complexes involved in NK cell homotypic adhesion., These results provide evidence that the activation of Rac2 by angiotensin II is exerted through multiple signalling pathways, involving Ca(2)(+)/calcineurin and protein kinases., In primary activated CD4(+) T cells, Rac1 and Rac2 were independently required for maximal TCR-induced apoptosis., DOCK2 and DOCK9 specifically recognize Rac2 and Cdc42 through their switch 1 as well as beta2-beta3 regions and the mode of recognition via switch 1 appears to be conserved among diverse Rac-specific DHR-2 GEFs, RAC2 is rarely mutated in gliomas, PI3K and Src-ELMO-Dock2 pathways work in parallel to activate Rac2 and modulate chemotaxis in response to a CXCL8 gradient in neutrophils., important in T cell immunological synapse assembly, Primary granule exocytosis in human neutrophils is regulated by Rac2-dependent actin remodeling., OAG-induced NOX2 activation was mediated by PKC and PI3K through the regulation of Rac2 activity, Rac1 and Rac2 are both required for efficient chemotaxis., Human neutrophils kill invading microbes while limiting oxidative damage to the adjacent surrounding healthy tissue through differential activation of Rac1 and Rac2 in response to different concentrations of chemoattractant., Data show that activation of PLCbeta(2) by alpha(q) and beta1gamma2 differ from activation by Rac2 and from each other., Rac1 and Rac2 GTPases are essential for normal bone marrow erythropoiesis, but they are dispensable for erythropoiesis in the spleen., Mutations in RAC2 GTPase have been found to cause a human disease, a severe phagocytic immunodeficiency characterized by lifethreatening infections in infancy. Review., LFA-1-induced stabilization of ARE-containing mRNAs in T cells is dependent on HuR, and occurs through the Vav-1, Rac1/2, MKK3 and p38MAPK signaling cascade, activated cells PLD2 affects Rac2 in an initial positive feedback, but as Rac2-GTP accumulates in the cell, this constitutes a "termination signal" leading to PLD2 inactivation., data reinforce recent evidences that susceptibility alleles/haplotypes are shared among multiple autoimmune disorders and support a causal role for RAC2 variants in the pathogenesis of autoimmune diseases., This variant reduced binding of the NCF2 gene product p67(phox) to RAC2. This study found a novel genetic association of RAC2 with Crohn's disease (CD) and replicated the previously reported association of NCF4 with ileal CD., The mRNA and protein levels of Rac1 and Rac2 are elevated following exposure of endothelial progenitor cells to the chemokine SDF-1alpha., CNF1 modified Rac2, which then interacted with the innate immune adaptors IMD and Rip1-Rip2 in flies and mammalian cells, respectively, to drive an immune response, Rac2 GTPase alters mitochondrial membrane potential and electron flow through the mitochondrial respiratory chain complex III, generating high levels of reactive oxygen species in chronic-phase CML stem cells and primitive leukemia progenitor cells., study identified several missense mutations for RAC1 and RAC2, with some of the mutant proteins, including RAC1(P29S), RAC1(C157Y), RAC2(P29L), and RAC2(P29Q), being found to be activated and transforming; activating mutations of RAC GTPases were thus found in a wide variety of cancers at a low frequency, findings indicate that a chemokine-controlled pathway, consisting of Galphai2, ELMO1/Dock180, Rac1 and Rac2, regulates the actin cytoskeleton during breast cancer metastasis, Mutations in hematopoiesis-specific Rho GTPases Rac2 and RhoH lead to a wide range of human blood disorders. (Review), p47(phox) and Rac2 accumulate only transiently at the phagosome at the onset of NADPH activity and detach from the phagosome before the end of reactive oxygen species production., These studies imply functional importance of iNOS and its interaction with Rac2 in pathogen killing by the neutrophils., homozygous loss-of-function RAC2 mutation in 2 patients with early-onset and progressive hypogammaglobulinemia(novel homozygous nonsense mutation in codon 56 (W56X)of RAC2 gene), our present analysis reinforces the involvement in ACT of the regulatory NADPH oxidase subunit RAC2 gene variant rs13058338 and, to a lesser extent of the CYBA gene variant rs4673., RAC2 specifically interacted with a set of mitochondrial proteins., RAC1/RAC2 and SFK are proximal and essential for phosphatidylinositol 3-kinase (PI3K) activation in NK cell-mediated direct cytotoxicity against Cryptococcus neoformans.,
OMIM_DISEASE Neutrophil immunodeficiency syndrome,
SP_COMMENT disease:Defects in RAC2 are the cause of neutrophil immunodeficiency syndrome [MIM:608203]., enzyme regulation:Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase., function:Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Seems to be involved in the regulation of the NADPH oxidase., online information:RAC2 mutation db, similarity:Belongs to the small GTPase superfamily. Rho family., subcellular location:Membrane-associated when activated., subunit:Interacts with DOCK2, which may activate it., tissue specificity:Hematopoietic specific.,
ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3)(RAC3) ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3)(RAC3) Related Genes Homo sapiens
CHROMOSOME 17,
CYTOBAND 17q25.3,
ENSEMBL_GENE_ID ENSG00000169750,
GENERIF_SUMMARY Our data is the first report of the frequency of Rac3 overexpression and mutation in human brain tumors. Overexpression may be associated with aggressive tumor behavior, functional analysis of Rac1 and Rac3 using RNA interference reveals a critical role for these GTPases in the invasive behavior of glioma and breast carcinoma cells, results suggest a role for both the Rac1 and Rac3 GTPases in human breast cancer progression, RAC1 and RAC3 have opposing functions in cell adhesion and differentiation in neuronal cells., Data demonstrate that Rac3 shares with Rac1 the ability to interfere with cadherin-mediated adhesion., Rac3 inhibits adhesion and differentiation of neuronal cells by modifying GIT1 downstream signaling., RAC3 is a novel ERalpha co-activator that promotes cell migration and has prognostic value for ERalpha-positive breast cancer metastasis., Rac3 GTPase has a role in the regulation of autophagy, RAC3 bound tightly to the ARE enhancer region of the HO-1 promoter via Nrf2 binding., Activation of epithelial-mesenchymal transition by MMP-induced expression of Rac1b gave rise to lung adenocarcinoma., Rac1b forms a complex with NADPH oxidase and promotes the production of reactive oxygen species, expression of Snail, and activation of the epithelial-mesenchymal transition program., Hypoxia inhibits the RAC3 gene expression leading to the autophagy process, allowing tumor cells to survive until angiogenesis occurs, Report role of Rac3 in breast cancer aggressiveness and show the potential usefulness of Rac3 depletion in breast cancer therapy., Collectively these data unveil that FBXL19 functions as an antagonist of Rac3 by regulating its stability and regulates the TGFbeta1-induced E-cadherin down-regulation., Efficient silencing of Rac3 strongly inhibited A549 cell proliferation., RAC3 is an inhibitor of senescence whose downregulation in aged individuals could be probably a tumor suppressor mechanism.,
SP_COMMENT function:Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as cell spreading and the formation of actin-based protusions including lamellipodia and membrane ruffles., induction:Expression down-regulated in quiescent fibroblasts and clearly induced by serum stimulation., similarity:Belongs to the small GTPase superfamily. Rho family., subcellular location:Membrane-associated when activated. Co-localizes with NRBP to endomembranes and at the cell periphery in lamellipodia., subunit:Interacts with the GEF protein DOCK7, which promotes the exchange between GDP and GTP, and therefore activates it. Interacts with C1D., tissue specificity:Highest levels in brain, also detected in heart, placenta and pancreas.,