Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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p21 (RAC1) activated kinase 1(PAK1) p21 (RAC1) activated kinase 1(PAK1) Related Genes Homo sapiens
CYTOBAND 11q13-q14,
GENERIF_SUMMARY Pak1 forms homodimers in vivo and its dimerization is regulated by the intracellular level of GTP-Cdc42 or GTP-Rac1, PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway., binding of the Rho family member Cdc42 to PLD1 and the subsequent stimulation of its enzymatic activity are distinct events, Pak1 interacts with and phosphorylates histone H3 and may thus influence the Pak1-histone H3 pathway, which in turn may influence mitotic events in breast cancer cells, FLNa may be essential for Pak1-induced cytoskeletal reorganization, Cdc42/Rac1-dependent activation of PAK may trigger early platelet shape change, at least in part through the regulation of cortactin binding to PAK., p21-activated kinase 1 (PAK1) interacts with the Grb2 adapter protein to couple to growth factor signaling, phorbol ester induced cell migration is accompanied by selective and transient down-regulation of PAK1, which coincided with the formation of stress fibres., role in phosphorylating Raf-1 regulates Raf-1 autoinhibition, results identify a novel signaling pathway linking estrogen action to Pak1 signaling, and Pak1 to FKHR, suggesting that Pak1 is an important mediator of estrogen's cell survival functions, 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., G beta gamma binds PAK1 and, via PAK-associated PIX alpha, activates Cdc42 which, in turn, activates PAK1. In this pathway, PAK1 is not only an effector for Cdc42, but it also functions as a scaffold protein required for Cdc42 activation., PAK1 regulates contact inhibition during epithelial wound healing., PAK1 copy number gains were observed in 30% of ovarian carcinomas and PAK1 protein was expressed in 85% of tumors. PAK1 gains were associated with high grade., Pak1 regulation of cyclin D1 expression might involve an NF-kappaB-dependent pathway; Pak1 is up-regulated in breast tumors, Tat induces actin cytoskeletal rearrangements through PAK1 in human umbilical vein endothelial cells, Phosphorylation of p41-ARC protein by p21-activated kinase 1., PAK2 is constitutively activated in certain breast cancer cell lines and that this active PAK is mislocalized to atypical focal adhesions in the absence of high levels of activated Rho GTPases., Src- & ROS-dependent PDK1 activation leads to site-specific PAK1 phosphorylation. This is critically important for PDGF-induced VSMC migration, a process integral to the vascular response to injury that leads to vessel occlusion & plaque formation., Pak-1 has a role in human colorectal tumor invasiveness and motility, These results support a role for Pak1-mediated RhoGDI phosphorylation as a mechanism for Cdc42-mediated Rac activation, and suggest the possibility of Rac-induced positive feed-forward regulation of Rac activity., PAK is a central regulator of endothelial permeability induced by multiple growth factors and cytokines via an effect on cell contractility, cell signaling kinase Pak1 is a novel regulator of glucose metabolism through its phosphorylation and regulation of PGM activity., NF-kappaB- and C/EBPbeta-driven interleukin-1beta gene expression and PAK1-mediated caspase-1 activation play essential roles in interleukin-1beta release from Helicobacter pylori lipopolysaccharide-stimulated macrophages, epithelial cell motility is modulated by integrin engagment through RhoA/ROCK and PAK1, PAK1 negatively regulates the activity of NET1, These findings define the nuclear localization signals (NLSs) of Pak1, its association with chromatin, and the resulting modulation of transcription, thus opening new avenues to further the search for nuclear Pak1 functions., ArgBP2gamma is a physiological substrate of Akt, functions as an adaptor for Akt and PAK1, and plays a role in Akt/PAK1 cell survival pathway, Pak1-SHARP interaction plays an essential role in enhancing the corepressor functions of SHARP, thereby modulating Notch1 signaling in human cancer cells., PAK1 phosphorylation of tubulin cofactor B (TCoB)is essential for the polymerization of new microtubules., The regulation of phosphorylation and function of Snail by Pak1 represents a novel mechanism by which a signaling kinase might contribute to the process of epithelial-mesenchymal transition., Pak1-dependent Raf-1 phosphorylation regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association, PAK1 recruitment to the T cell-antigen-presenting cell interface required interaction with PIX., 1.8 A resolution structure for the free PAK1 kinase domain was determined., Data suggest that nischarin, in addition to regulating the p21-activated kinase (PAK) strand of Rac1 signaling, can also regulate other links in the web of Rac1 signaling pathways., p21-activated kinase 1 has a role in the suppression of anoikis in breast cancer cells, the SH3 domain of betaPix specifically interacts with a proline-arginine motif (PxxxPR) present within the ubiquitin ligase Cbl and Pak1 kinase. Cbl and Pak1 compete for binding to betaPix., Results show that PAK1 cooperate with different Rho effectors to regulate matrix contraction., PI3K through p21-activated kinase 1 regulates FRA-1 proto-oncogene induction by cigarette smoke and the subsequent activation of the Elk1 and cAMP-response element-binding protein transcription factors, Myosin II-B resides in a complex with p21-activated kinase 1 (PAK1) and atypical protein kinase C (PKC) zeta (aPKCzeta) and the interaction between these proteins is EGF-dependent., Our data support a role for Pak1, particular Pak1 localized to the nucleus, in ERalpha signaling and in tamoxifen resistance., Phosphorylation of caldesmon by PAK is a dynamic process required to regulate actin dynamics and membrane protrusions in wound-induced cell migration., Increased p21-activated kinase-1 expression is associated with invasive potential in uveal melanoma, Akt1 and Akt2 have opposing roles in Rac/Pak signaling and cell migration, TGF-ss, via PI3K, recruits the actin cytoskeleton to HER2, which colocalizes with Vav2, activated Rac1, & its effector Pak1 at lamellipodia, leading to prolonged Rac1 activation, enhanced cell motility & survival. Dominant-negative Pak1 abrogates this., p70 S6 kinase activates PAK1 and contributes to phosphatidylinositol 3-kinase- and ERK-mediated regulation of HCV RNA replication, Results demonstrate a novel mechanism of signal termination mediated by the Rho-family GTPases Chp and Cdc42, which results in ubiquitin-mediated degradation of one of their direct effectors, Pak1., PAK1 is a physiological upstream kinase for integrin-linked kinase (ILK); PAK1 depletion dramatically increases the nuclear and focal point accumulation of ILK., Amplification of PAK1 is associated with recurrence and tamoxifen resistance in postmenopausal breast cancer, ESE-1 functions are coordinately regulated by Pak1 phosphorylation and beta-TrCP-dependent ubiquitin-proteasome pathways., we present a model for Pak1 signaling that provides a mechanism for specifically affecting cardiac cellular processes--REVIEW, point to Pak1 as an exciting target for therapy of renal cancer, which remains highly refractory to existing treatments, study reports that elevated (alpha6)beta4 integrin-dependent Rac-Pak1 signaling supports resistance to apoptosis in mammary acini by permitting stress-dependent activation of the p65 subunit of NF-kappaB through Pak1, Rac1/Pak1/LIMK1 signaling pathway controls cofilin activity within the lamellipodium., 16k PRL inhibits cell migration by blocking the Ras-Tiam1-Rac1-Pak1 signaling pathway in endothelial cells, Pak1 overexpression enhanced htt toxicity in cell models and neurons in parallel with its ability to promote aggregation, while Pak1 knockdown suppressed both aggregation and toxicity, a VAV1-Rac1-PAK1 signaling axis in mononuclear phagocytes regulating superoxide production in a stimulus-dependent manner., In an ovarian carcinoma cohort, RSF1 was amplified in 15% of the cases. It was correlated with serous histology. The 11q13 amplicon in ovarian cancer is likely driven by a cassette of genes rather than by a single oncogene., The data indicate that PAK1 is at the interface between junction destabilization and increased motility during morphogenetic events., Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1, Pak1 and Pak2., p21-activated kinase-aberrant activation and translocation may have a role in Alzheimer disease pathogenesis, These results provide an insight into the molecular mechanisms of CtBP1/BARS activation in membrane fissioning, and extend the relevance of CtBP1/BARS-induced fission to human viral infection., Overexpression of p21-activated kinase 1 may be a key coordinator of aberrant cell survival and proteolysis in breast cancer progression., Pak1 and Pak2 mediate tumor cell invasion through distinct signaling mechanisms, alpha2beta1 integrin clustering defines its own entry pathway that is Pak1 dependent but clathrin and caveolin independent and that is able to sort cargo to caveosomes, 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., In Cox analysis, higher p21-activated kinase-1 staining extent independently correlated with longer progression-free survival (P = .016) and shorter overall survival (.049) in primary diagnosis and disease recurrence effusions., PAK1-specific paxillin phosphorylation at Ser(273) is critically involved in positive-feedback regulation., Data examine possible allelic imbalance in papillary thyroid cancer at EMSY, CAPN5, and PAK1, as candidate genes within 11q13.5-q14 region using a single nucleotide polymorphism-based analysis., Pak1 is a target of miR-7 and that HoxD10 plays a regulatory role in modifying the expression of miR-7., Expression of active p21-activated kinase-1 induces Ca2+ flux modification with altered regulatory protein phosphorylation in cardiac myocytes., TH1 interacts with PAK1 and specifically restricts the activation of MAPK modules through the upstream region of the MAPK pathway, thereby influencing cell migration., Pak1 protein plays a critical role in Hepatocyte Growth Factor-induced WASF2 protein transport and lamellipodia formation by directing Pak1 protein-WASF2 protein-kinesin complex., Pak protein kinases have a role in cancer [review], Overexpression of PAK1 protein is closely associated with the malignant histological and invasive phenotype of colorectal carcinoma., We identified a novel mechanism for MMP-9 expression in response to injury signals, which is mediated by PAK1 activation, study identified p21 activated kinase 1 (PAK1) as a new CDK11(p58) substrate; mapped a new phosphorylation site of Ser174 on PAK1; results indicated PAK1 may serve as a downstream effector of CDK11(p58) during mitosis progression, LC8 facilitates nuclear import of Pak1 and this function is indispensable during vertebrate development, a model for the complex and accurate regulation of PAK1 kinase in vivo at cell protrusions., Overexpression of Pak1 was associated with progression, metastasis and prognosis of gastric cancer., Knockdown of PAK1 inhibits Hepatocyte Growth Factor (HGF) stimulated migration and loss of cell-cell junctions in DU145 prostate carcinoma cells. In PC3 prostate carcinoma cells, knockdown of PAK1 reduces HGF-stimulated migration., Basic properties of group I Paks are summarized discuss recently uncovered roles for these kinases in immune function and in viral infection are discussed., 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., 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., A possible role of Pak1 in the establishment of adenomyosis., 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., Our results suggest that patients with tumors expressing Pak1 and pERalpha(ser305) in combination are a group in which tamoxifen treatment is insufficient, PKA-induced phosphorylation of ERalpha at serine 305 and high PAK1 levels is associated with sensitivity to tamoxifen in ER-positive breast cancer., PAK1 is a direct downstream target of LKB1 and plays an essential role in LKB1-induced suppression of cell migration, Data reveal the involvement of p21-Activated kinase 1 in the pathogenesis and clinical progress of gestational trophoblastic disease., A functional requirement for PAK1 binding to the KH(2) domain of the fragile X protein- related FXR1 is reported., 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., Pak1-induced branching morphogenesis in 3D MDCK cell culture requires PIX binding and beta1-integrin signaling., Rac1/Cdc42/PAK pathway controls actin reorganization that is necessary for microvesicle shedding, Rac1/Pak1 signaling is critical to MB cell migration and is functionally dependent on PDGFRbeta/ERK activity, Expression of PAK1 is an early molecular event in the tumorigenesis of gastric carcinoma. It is also closely correlated the development of gastric carcinoma and the patients' prognosis., P21-activated kinase 1 stimulates colon cancer cell growth and migration/invasion via ERK- and AKT-dependent pathways., Data show that the protective effects of atrial natriuretic peptide against lipopolysaccharide-induced vascular leak are mediated at least in part by PAK1-dependent signaling leading to endothelial cell barrier enhancement., Results suggest that activated Pak1 regulates colorectal cancer metastasis requiring an ERK-dependent phosphorylation of FAK at Ser-910., These findings expand the role of phosphoinositides in kinase signaling and suggest how altered phosphoinositide metabolism may upregulate Pak1 activity in cancer cells., the PI3K/PAK1/ERK signaling pathway has a role in LPA-stimulated breast cancer cell migration, The importance of PIK3K/PAK in neoplasm transformation and progression, their disregulation detected in oral squamous cell carcer may provide early diagnosis and aid in the design of new therapies., Contribution of the PAK family member, PAK1, in growth factor signaling and tumorigenesis., Adapter protein Nck sequesters PAK1 in the cytoplasm and that coexpression of both PAK1 and Nck inhibits the amplifying effect of PRL-induced PAK1 on cyclin D1 promoter activity., Interleukin-1beta up-regulates Pak1 expression in endometrial stromal cells and Pak1 immunoreactivity is increased in endometriotic cysts., increased activation of associated PAK1 can contribute to enhanced Cx43 dephosphorylation and impaired intercellular coupling that may underlie slow conduction in heart failure, results suggest that CIB1 positively regulates cell migration and is necessary for the recruitment of FAK to the focal adhesions. Furthermore, CIB1-induced cell migration is dependent on MAP kinase signaling and its function is attenuated by PAK1, a Rac1/PAK1 cascade controls beta-catenin S675 phosphorylation and full activation in colon cancer cells, Inhibition or ablation of p21-activated kinase (PAK1) disrupts glucose homeostatic mechanisms in vivo., These results provide evidence for the importance of PAK1 activation during influenza virus infection and its association with ERK in regulating virus replication., Findings demonstrate that Pak1 phosphorylates BAD directly at S111, but phosphorylated S112 through Raf-1., In colorectal neoplasms p-21 activated kinase 1 knockdown inhibits beta-catenin signalling and blocks cell proliferation and migration., A Rac-PAK1-Ajuba feedback loop integrates spatiotemporal signaling with actin remodeling at cell-cell contacts and stabilizes preassembled cadherin complexes., PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, Smad4 suppresses the PAK1, which promotes the PUMA destabilization, crystal structures of the phosphorylated and unphosphorylated PAK1 kinase domain., Data suggest that targeting P21-activated protein kinase1 (PAK1) may represent a novel treatment strategy for developing novel chemotherapeutic agents., Pak1 is overexpressed in gastric cancer and plays an important role in the metastasis of gastric cancer. The mechanism by which Pak1 induces cancer metastasis may involve activation of ERK and JNK., these results provide evidence that PAK1 specifically phosphorylates beta-catenin at S663 and that this phosphorylation is essential for the PAK1-mediated transcriptional activation of beta-catenin., PAK1 plays an important role in regulating the migration, invasion and production and activity of MMPs in RA FLS, which is mediated by the JNK pathway., In both anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC), study found a reduction of Duo expression and PAK1 phosphorylation in schizophrenia. Cdc42 protein expression was decreased in ACC but not in DLPFC, results show that a STRADalpha-rac1-PAK1 pathway regulates cell polarity and invasion in LKB1-null cells. It also suggests that while the function of LKB1 and STRADalpha undoubtedly overlap, they may also have mutually exclusive roles, PI3K, Rac1 and PAK1 may play important roles in the pathogenesis of EMPD., the role of PAK1 in the promotion of cell motility, cell invasiveness and the down regulation of p120-catenin through CRK serine 41 phosphorylation in NSCLC cells, In the title., Results show a strong positive correlation between advanced stage and grade and PAK1 expression in skin cnacer., Phosphoproteome analyses reveal specific implications of Hcls1, p21-activated kinase 1 and Ezrin in proliferation of a myeloid progenitor cell line downstream of wild-type and ITD mutant Fms-like tyrosine kinase 3 receptors., Pak-1 interacts with Wnt signaling to regulate tissue polarity and gene expression., PAK1 negatively regulates the expression of TFPI and additionally contributes to increased TF activity., PAK1 phosphorylates MCAK and regulates both its localization and function., Results support a role for the PAK4 and PAK1 in the proliferation of mutant KRAS-driven colorectal carcinoma cells via pathways not involving RAF/MEK/ERK and PI3K/AKT signaling., data suggest that glucose-mediated activation of Cdc42 leads to activation of PAK1 and prompts activation of its downstream targets Raf-1, MEK1/2 and ERK1/2 to elicit F-actin remodeling and recruitment of insulin granules to the plasma membrane, Gene array data revealed reduced expression of matrix metalloproteinase 9 with the ablation of either Pak1 or Pak6 gene expression in PC3 cells., 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., High expression of the PAK1 gene was significantly associated with resistance to all three PI3K inhibitors in lymphomas., Data suggest that regulation of PAK-PIX interactions controls neurite outgrowth by influencing the activity of several important mediators of actin filament polymerization and retrograde flow, as well as integrin-dependent adhesion to laminin., these findings demonstrate that miR-221 affects the MEK/ERK pathway by targeting PAK1 to inhibit the proliferation ofendothelial progenitor cells., These results suggest that Pak1 plays important roles at multiple stages of EC progression., PAK1 phosphorylates serine (Ser) 2152 of the actin-binding protein filamin A to a greater extent when PAK1 is tyrosyl phosphorylated by JAK2., analysis of synergistic activation of p21-activated kinase 1 by phosphatidylinositol 4,5-bisphosphate and Rho GTPases, Cytokine-induced migration correlated with phosphorylation of PAK1 in primary myeloma cells & cell lines. Downregulation of PAK1 with siRNA in INA-6 cells resulted in decreased cytokine-driven migration., Klotho endows hepatoma cells with resistance to anoikis via VEGFR2/PAK1 activation in hepatocellular carcinoma., Taken together, our results provide evidence for a functional role of PAK1 in BRAF wild-type melanoma and therapeutic use of PAK inhibitors in this indication., Data indicate a signaling pathway from ErbB2 to p21-Activated kinase-1 (Pak1) to beta-catenin that is required for efficient transformation of mammary epithelial cells., no significant change in PAK1 level detected in the schizophrenia subjects, Group I p21-activated kinases augment Tax-mediated transcriptional activation of human T-cell leukemia virus type 1 long terminal repeats in a kinase-independent manner., PAK1 can stimulate MEK activity in a kinase-independent manner, probably by serving as a scaffold to facilitate interaction of C-RAF., Data indicate that depletion of NFATc1, cyclin D1, CDK6, or CDK4 levels attenuated MCP1-induced Pak1 phosphorylation/activation and resulted in decreased aortic smooth muscle cells (HASMCs) F-actin stress fiber formation, migration, and proliferation., These data illustrate the complex interaction between the substratum and PRL/PAK1 signaling in human breast cancer cells and suggest a pivotal role for PRL-dependent PAK1 tyrosyl phosphorylation in MMP secretion., PAK1 stimulates colorectal cancer cell survival by up-regulation of HIF-1alpha., The results identified Mgat5-mediated beta-1-6-GlcNAc branched N-glycosylation and following activation of EGFR as a potential novel upstream molecular event for PAK1-induced anoikis resistance in hepatoma cells., These findings identify CK2 as an upstream activating kinase of PAK1, providing a novel mechanism for PAK1 activation., PAK1 is overexpressed during tumorigenic progression and its upregulation correlates with malignant properties mainly relevant to invasion and metastasis., blocking PI3K/Akt signaling pathway by LY294002 or Akt siRNA could remarkably inhibit the PAK1 activation and cell invasion, identified fibronectin, a component of the extracellular matrix and a mesenchymal marker, as a transcriptional target of Pak1 signaling, PAK1 is associated with the aggressive tumor behavior and poor prognosis of head and neck cancer., Review of the role of PAK1 in gastrointestinal inflammation and progression to cancer., Describe here an invadopodia disassembly model, where a signalling axis involving TrioGEF, Rac1, Pak1, and phosphorylation of cortactin, causes invadopodia dissolution., Amplified PAK1, as well as KRAS amplification/mutation, may represent unique opportunities for developing targeted therapeutics for the treatment of gastric cancer., Data indicate that p21-activated kinase 1 (PAK1) is a target of miR-145., PAK1 and Snail1 are involved in the formation of estrogen-independent phenotype of breast cancer cells showing the potential role of both proteins as markers of hormone resistance of breast tumors., results provide evidence for a functional role of MET/PAK1 signalling in pancreatic adenocarcinoma, findings offered evidence that JAK2 phosphorylates and stabilizes functions of PAK1 that promote EMT and radioresistance in lung cancer cells, high PAK1 expression in PTs is predictive of node metastasis and can be easily integrated in the clinical decision process for personalized therapeutics of GEJA., PAK1 is a novel prognostic marker for pathologically confirmed human pancreatic cancer. Reduced expression of PAK1 correlates with poor histological differentiation in pancreatic cancer., PAK1 is an essential controller of inflammatory macrophage polarization, regulating immune responses against pathogenic stimuli., Increased p21-activated kinase is associated with invasive papillary thyroid cancers., Moreover, the up-regulation of Axl was induced by TGF-beta1, further activated phosphatidylinositol 3-kinase (PI3K)/Akt and PAK1 translocation, and resulted in greater cell motility, invasion, and chemoresistance in vitro and in vivo, Provide first evidence for existence of a previously unknown Erk5/KLF2/PAK1 axis, which may limit undesired cell migration in unperturbed endothelium and lower its sensitivity for migratory cues that promote vascular diseases including atherosclerosis., we demonstrated that the overexpression of PAK1 is closely associated with the clinicopathological features of BC, suggesting that PAK1 may play an important role in the development and progression of Bladder cancer, Studies indicate a p21-activated kinase PAK1 inhibitor series were discovered., PAK1 role in cardiac physiology such as egulation of cardiac excitability and contractility has been identified., miR-221-3p has an effect on PAK1 gene expressions in breast cancer cell lines, These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis., High Phosphorylation of tyrosine 285 of PAK1 protein is associated with breast cancer., A pivotal role for PRL/PAK1 signaling in breast cancer metastasis.[review], Overexpression of PAK1 promotes cell survival in inflammatory bowel diseases and colitis-associated cancer., Data show that group I p21-activated kinases (Paks) Pak1 and Pak2 were much more abundant than Pak3 in meningioma., results unraveled that oncogenic activation of PAK1 defines an important mechanism for maintaining stem-like phenotype and sunitinib resistance through NF-kappaB/IL-6 activation in RCC., TGFbeta1 induces apoptosis and epithelial-mesenchymal transition in prostate cancer cells via activation of P38-MAPK and Rac1/Pak1 respectively., these findings provide important evidence that PAK1 can positively regulate RUFY3 expression, which contribute to the metastatic potential of gastric cancer cells, PAK1 and PAK4 expression were associated with colorectal cancer metastasis and infiltration, PAK1-mediated MORC2 phosphorylation promotes gastric tumorigenesis, Studied the role of PAK1/Crk axis in transduction of the oncogenic KRAS signal in non-small cell lung cancer (NSCLC)., This study showed that PAK1 messenger RNA levels were significantly downregulated specifically in deep layer 3 pyramidal cells in patient with schizophrenia., Rich1 negatively regulates the epithelial cell cycle, proliferation and adhesion by CDC42/RAC1-PAK1-Erk1/2 pathway., Study indicates that PAK1 is important in metastasis and progression of primary esophageal small cell carcinoma. The contribution of PAK1 to clinical outcomes may be involved in regulating DNA damage pathway., PAK1 overexpression and activation in inflammation and colitis-associated cancer promote NF-kappaB activity via suppression of PPARgamma in intestinal epithelial cells., Pak1 and Pak2 counteract centrosome separation in a kinase-dependent manner., Pak1 is an important factor in the initiation and progression of atherogenesis., There is a major role of the CK2alpha-interacting protein CKIP-1 in activation of PAK1 for neoplastic prostate cells transformation., Pak1 promote endometrial cancer cell proliferation., Cx43 increases serum induced filopodia formation via activation of p21-activated protein kinase 1., These findings indicate that genetic variants in PAK1 gene may contribute to susceptibility to lung cancer in the Chinese population., beta-elemene enhances radiosensitivity of gastric cancer cells by inhibiting Pak1 signaling., Data indicate that NOTCH1 receptor intracellular domain (NOTCH1-IC) physically interacts with serine-threonine-protein kinase PAK 1 (PAK1) in intact cells., Combination of a PAK1 inhibitor such as FRAX597 with cytotoxic chemotherapy deserves further study as a novel therapeutic approach to pancreatic cancer treatment., Formation of filopodia by membrane glycoprotein M6a (Gpm6a) requires actin regulator coronin-1a (Coro1a), known to regulate plasma membrane localization and activation of Rac1 and its downstream effector Pak1., PAK1 nuclear translocation is ligand-dependent, Data show association of G protein-coupled receptor kinase-interacting protein 1 (GIT1), p21-activated kinase interacting exchange factor (betaPIX), and p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1) with centrosomes.,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., cofactor:Magnesium., enzyme regulation:Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-423 and allows the kinase domain to adopt an active structure. Also activated by binding to GTP-bound CDC42, independent of the phosphorylation state of Thr-423. Phosphorylation of Thr-84 by OXSR1 inhibits this activation., function:The activated kinase acts on a variety of targets. Likely to be the GTPase effector that links the Rho-related GTPases to the JNK MAP kinase pathway. Activated by CDC42 and RAC1. Involved in dissolution of stress fibers and reorganization of focal complexes. Involved in regulation of microtubule biogenesis through phosphorylation of TBCB. Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2., PTM:Autophosphorylated when activated by CDC42/p21 and RAC1., similarity:Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily., similarity:Contains 1 CRIB domain., similarity:Contains 1 protein kinase domain., subcellular location:Recruited to focal adhesions upon activation., subunit:Homodimer in its autoinhibited state. Active as monomer. Interacts tightly with GTP-bound but not GDP-bound CDC42/P21 and RAC1. Binds to the caspase-cleaved p110 isoform of CDC2L1 and CDC2L2, p110C, but not the full-length proteins. Component of cytoplasmic complexes, which also contain PXN, ARHGEF6 and GIT1. Interacts with ARHGEF7. Also interacts with CRIPAK. Interacts with NISCH.,