Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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paxillin(PXN) paxillin(PXN) Related Genes Homo sapiens
CYTOBAND 12q24.31,
GENERIF_SUMMARY Binding of Paxillin to the alpha 9 Integrin Cytoplasmic Domain Inhibits Cell Spreading., expression in conventional renal cell carcinomas (RCCs), papillary RCCs, chromophobe RCCs, collecting duct carcinomas, oncocytomas; role in signal transductions as a focal adhesion between tumor cells and the ECM in tumors with collecting duct phenotypes, Tyrosine phosphorylation of PXN regulates localization and downstream signaling with profound effects on cell movement., Binding of cytoskeletal paxillin to the C-terminal of Pyk2 in cultured human umbilical vein endothelial cells is phosphorylation-independent and is not affected by acute exposure to thrombin., Amino acid substitutions at relevant serine residues in urokinase prevents paxillin redistribution in MCF-7 cells., Paxillin binding to the alpha 4 integrin tail is required for both efficient communication between integrins alpha 4 beta 1 and alpha L beta 2 and for direct integrin alpha 4 beta 1-dependent T cell migration., Integrin alpha 4 beta 1-dependent T cell migration requires both phosphorylation and dephosphorylation of the alpha 4 cytoplasmic domain to regulate the reversible binding of this protein., phosphorylation of paxillin by JNK seems essential for maintaining the labile adhesions required for rapid cell migration, interaction of bcl-2 with paxillin plays an important role during nephrogenesis, Data show that phosphorylation of paxillin is involved in NGF-induced neurite extension of PC-12 cells, probably through regulating focal adhesion organization., RhoA/Rho-kinase pathway followed by tyrosine phosphorylation of FAK and paxillin leads to ATP release and actin reorganization in vascular endothelium, Lysophosphatidic acid induces Rho activation and consequent tyrosine phosphorylation of paxillin in human corneal epithelial cellss. Likely contributes to promotion of corneal epithelial migration by this agent., early spreading responses to HGF may partly relate to increased paxillin availability for incorporation into, and turnover within, dynamic cytoskeletal/membrane complexes whose rapid and transient adhesion to the matrix drives migration., chemoattractant stimulation induces paxillin association with alpha4 integrins, particularly in leukocytes, paxillin tyrosine 31 and 118 phosphorylation controls polarization and motility of lymphoid cells and is PMA-sensitive, Myocilin impaired focal adhesion formation and specifically blocked the incorporation of paxillin, but not vinculin, into focal adhesions., Angiotensin II mediates an increase in focal adhesion kinase and paxillin phosphorylation and induces human umbilical vein endothelial cells migration through signal transduction pathways, Expression of paxillin and syndecan-1 in hepatocellular carcinoma(HCC) may affect its invasive and metastatic ability. May be converse correlation between expression of paxillin and syndecan-1 protein in HCC., Caco-2 migration on collagen IV is regulated by both p130cas and paxillin but Src phosphorylation of p130cas is more important for this process, overexpression of paxillin synergistically contribute to the high metastatic potential of human osteosarcoma through the hyperphosphorylation of paxillin, p130Cas and paxillin function as effectors of GD3-mediated signaling, leading to such malignant properties as rapid cell growth and invasion in melanoma cells, proteomic analysis of paxillin post-translational modifications and interacting proteins by mass spectrometry, Alpha4beta1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha4-cytoplasmic domain, Metastasizing squamous cancer cell adhesiveness may be increased by paxillin-overexpression or by paxillin activation by extracellular pressure during surgical manipulation or growth within a constraining compartment., Our results indicate that Src maintains fibronectin matrix at the cell surface through its effect on integrin activity and paxillin phosphorylation., Hic-5 and paxillin function as negative feedback regulators of Src family kinases in aggregated platelets, study reports paxillin is phosphorylated in response to fibronectin-bound group A Streptococcus that express either M1 or PrtF1/SfbI protein; integrin-linked kinase activity is indispensable for M1-induced paxillin recruitment and phosphorylation, analysis of paxillin and ponsin interaction in nascent costameres of muscle cells, 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., These findings support a novel role for RACK1 as a key regulator of cell migration and adhesion dynamics through the regulation of Src activity, and the modulation of paxillin phosphorylation at early adhesions., Invadopodia ring expansion is controlled by paxillin phosphorylations on tyrosine 31 and 118, which allows invadopodia disassembly., Focal adhesion kinase as well as p130Cas and paxillin should be a crucial molecule undergoing stronger tyrosine phosphorylation in GD3-expressing melanoma cells., These results establish an important role for paxillin in lung cancer., Tissue factor pathway inhibitor prevented paxillin/focal adhesion kinase phosphorylation in endothelial cells to influence angiogenesis., No correlation occurs with clinocopathological parameters of esophageal squamous cell carcinoma,nor is paxilcillin an effective prognositic marker in these patients., Data show that genetic upregulation of matriptase-2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo and affects FAK and paxillin localisation., the alpha-parvin CH2-paxillin LD1 complex has a role in for focal adhesion assembly, analysis of PAFR activation and pleiotropic effects on tyrosine phospho-EGFR/Src/FAK/paxillin in ovarian cancer, These data show a dual role of paxillin in the HGF- and VEGF-mediated endothelial barrier regulation and suggest essential paxillin role in the modulation of Rac-Rho crosstalk., PAK1-specific paxillin phosphorylation at Ser(273) is critically involved in the positive-feedback regulation of the Rac-PAK1 pathway., These results suggest that phosphorylation of paxillin on Ser 178 by JNK is required for the association of paxillin with FAK, and subsequent tyrosine phosphorylation of paxillin., 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., analysis of JNK-mediated phosphorylation of paxillin in adhesion assembly and tension-induced cell death by the adenovirus death factor E4orf4, An unusual degree of binding degeneracy in the paxillin/alpha-parvin system that may facilitate the assembly of dynamic signaling complexes in the cell., Expression of nuclear-localized paxillin LIM domains stimulate DNA synthesis and cell proliferation, PGE2 greatly induced hepatocellular carcinoma cell adhesion, migration, and invasion by activating FAK/paxillin/Erk pathway., Data show that CXCL8 stimulation leads to paxillin phosphorylation in normal neutrophils, and that both CXCL8 receptors (CXCR1 and CXCR2) mediate CXCL8-induced paxillin phosphorylation., We found PXN polymorphisms including nonsynonymous ones but no PXN amplification and only 1/159 (<1%) somatic tumor mutation F416L, These results demonstrate that Pyk2 is constitutively associated with paxillin, that neither Tyr-881 nor kinase activity is necessary for the Pyk2/paxillin association, and that paxillin is a substrate of Pyk2 kinase., An integrin-alpha4-14-3-3zeta-paxillin ternary complex mediates localised Cdc42 activity and accelerates cell migration., Direct binding of toxin A to Src, independent of any effect on protein tyrosine phosphatase or Rho glucosylation, inhibits Src kinase activity followed by FAK/paxillin inactivation, These results suggest a novel mechanism for selective reinforcement of nascent adhesions via interplays of Nudel and FAK with paxillin to facilitate cell migration, enhanced expressions of HAb18G/CD147, MMPs, paxillin and FAK changed the distributions of cytoskeleton in the 3D reconstituted basement membrane (BM) and increased the adhesion and invasion potentials of hepatocellular carcinoma cells, MPS-1 reduces paxillin mRNA and protein levels in head-and-neck squamous-cell carcinoma cells both in vitro and in vivo., Using lung adenocarcinoma samples and cell lines derived from lung adenocarcinomas, we demonstrated that the gene copy number for MET in lung adenocarcinoma tissue samples was increased over EGFR, HGF, and PXN and that it correlated with better prognosis, leupaxin functions as a paxillin counterpart that potently suppresses the tyrosine phosphorylation of paxillin during integrin signaling., a small molecule that inhibits the interaction of paxillin and alpha 4 integrin inhibits accumulation of mononuclear leukocytes at a site of inflammation, Adhesion of ST6Gal I-mediated human colon cancer cells to fibronectin contributes to cell survival by integrin beta1-mediated paxillin and AKT activation., Data show that paxillin is a direct substrate of PTPRT and that PTPRT specifically regulates paxillin phosphorylation at tyrosine residue 88(Y88)., paxillin expression upregulated in SACC. High expression of paxillin correlated with more advanced stage and metastasis in SACC. paxillin is possibl disease marker in advanced SACC and SACC with distant metastasis. Possible value as therapeutic target, Paxillin silencing by RNA interference inhibits the cell invasiveness stimulated by fibronectin. Paxillin is a key factor in the fibronectin-stimulated invasiveness of AGS cells., The expression of paxillin may play an important role in human breast cancer metastasis and adhesion., Data describe the role of the IGF-IR in bladder cancer and show that it required the activation of the Akt and MAPK pathways as well as IGF-I-induced Akt- and MAPK-dependent phosphorylation of paxillin., cytohesin-2, through a previously unexplored complex formation with paxillin, regulates preadipocyte migration; paxillin plays a previously unknown role as a scaffold protein of Arf guanine-nucleotide exchange factor, paxillin may regulate prostate cancer proliferation by serving as a liaison between extra-nuclear kinase signaling and intra-nuclear transcriptional signals., GDF-9 can promote the motile and adhesive capacity of PC-3 prostate cancer cells by up-regulating expression of FAK and paxillin in a Smad dependent manner, suggesting a pro-tumourigenic role for GDF-9 in prostate cancer., Expressed in most neuroendocrine tumors of lung. Significant correlation between PAX5 and paxillin was detected in SCLCs and large cell neuroendocrine carcinomas but not in carcinoid tumors., New results confirmed that human cytomegalovirus entry into target monocytes was significantly reduced in cells deficient in paxillin expression or the integrin/Src/paxillin signaling pathway., Paxillin is a key regulator of 3D adhesion assembly, stabilization and disassembly., a novel role for calpain-mediated proteolysis of paxillin as a negative regulator of focal adhesion dynamics and migration that may function to limit cancer cell invasion., Differential requirement of adapter proteins paxillin and T cell linker (LAT) for responses to beta2 integrin (LFA-1) and CD16 are important for different signaling complex assemblies of signaling molecules to determine functional outcomes., When myosin II contractility was inhibited, the k(off) values for all three proteins changed rapidly, in a highly protein-specific manner, The expression of paxillin showed no correlation with estrogen/progesterone and HER2 expression nor with tumor grade and stage in breast carcinomas., In contrast to a previous report, this study showed that PXN mutation was absent in lung cancers and other common solid cancers, suggesting that PXN mutation may not play a principal role in solid cancer development., the crystal structures of CCM3 in complex with three different leucine-aspartate repeat (LD) motifs (LD1, LD2, and LD4) from the scaffolding protein paxillin, Down-regulation of paxillin is associated with autism., We propose paxillin as a novel cellular target for converging H. pylori-induced EGFR, FAK/Src, and PI3K/Akt signaling to regulate cytoskeletal reorganization and IL-8 production in part, thus contributing to the H. pylori-induced diseases., Talin-1 and vinculin negatively affect tyrosine phosphorylation of paxillin, a novel positive regulator of HIV-1 infection, and impose an early block to infection by distinct retroviruses., ezrin and paxillin may have roles in aggressive tumor features and invasiveness in urothelial bladder tumors, Paxillin enables attachment-independent tyrosine phosphorylation of focal adhesion kinase and transformation by RAS, paxillin may play an essential role in the progression of colorectal cancer., paxillin and FAK mRNA expression levels were significantly correlated with the differentiation degree and depth of invasion of esophageal carcinoma and with lymph node metastasis, Hypoxia can induce the activation of cytoplasmic FAK, Grb2 and paxillin so as to regulate the migration, survival and proliferation of pulmonary artery smooth cells., plays a critical role in neutrophil transmigration, Paxillin integrates physical and chemical motility signals by spatially constraining where cells will form motile processes, and thereby regulates directional migration., these results suggest that paxillin is required for the early phase of EC orientation in response to cyclic stretching by scaffolding for accumulation of focal adhesion proteins., The paxillin plays vital roles in cell motility through regulation of focal adhesion dynamics., paxillin is a liaison between extranuclear MAPK signaling and nuclear transcription in response to androgens and growth factors, Findings suggest that the MLK3-JNK-paxillin signaling axis may represent a potential prognostic marker in breast cancer metastasis., analysis of paxillin domains interacting with beta-catenin, cell adhesion-dependent Ser-85 phosphorylation of paxillin is important for its interaction with talin and regulation of dynamic FAs and cell migration., proper localization of beta-parvin to focal adhesions requires both the paxillin and integrin-linked kinase binding sites and that paxillin is important for early targeting of beta-parvin., phosphorylation of GIT1 on serine 46 by PKD3 represents a molecular switch by which GIT1 localization, paxillin trafficking, and cellular protrusive activity are regulated., Paxillin is a new regulator protein of pulmonary arterial smooth muscle cell growth., Paxillin is critical for integrating physical cues from the ECM with chemical motility signals by spatially constraining where cells form motile processes, and thereby regulates directional migration., Mutation of paxillin serine 250 prevents its phosphorylation by SLK in vitro and results in impaired migration in vivo as evidenced by an accumulation of phospho-FAK-Tyr397 and altered FA turnover rates., Rap1 can induce cell adhesion and stimulate an accelerated rate of cell spreading through mechanisms that bypass the canonical FAK-Src-Paxillin signalling cascade, Fascin-1, ezrin and paxillin contribute to the malignant progression and are predictors of clinical prognosis in laryngeal squamous cell carcinoma., overexpression of PXN induced by suppression of miR-137 promotes tumor progression and metastasis and could serve as an independent prognostic indicator in colorectal cancer patients., Data indicate that lasp-2 interacts with the focal adhesion proteins vinculin and paxillin., Paxillin signaling contributed to tumor growth and vasculogenic mimicry of gallbladder carcinomas., The data suggests that mutant PXN variants play a prominent role in mitochondrial dynamics with direct implications on lung cancer progression., the inhibitory effect of cAMP on migration, ruffling, focal adhesion dynamics and paxillin localisation is mediated by PKA, whilst EPAC potentiates migration., Lysophosphatidic acid (LPA) induces both time and dose-dependent tyrosine phosphorylation of paxillin and focal adhesion kinase., Study provides evidence that phosphorylation of PXN is required for cisplatin resistance in lung cancer cells., PXN plays an important role in tumor progression and may be used as a potential prognostic indicator in gastric cancer, Future studies investigating these hypotheses on TG-2-paxillin relationships are necessary in order to address this fundamental process in cell matrix adhesion signaling., In aneuploid tumors, EZH2 expression and paxillin expression correlate with more aggressive phenotype of breast cancer., The expression levels of Wnt5a, p-JNK1 and p-paxillin in tumor tissues were correlated with each other., paxillin may promote cell proliferation and inhibit apoptosis in SW480 cells. Paxillin may be a potential metastasis predictor, and an independent prognosis factor of recurrence., Paxillin knockdown increases capillary endothelial cell migration and invasiveness, and thereby enhances microvessel ingrowth, by suppressing NRP2 expression., Colocalisation of FAK and paxillin supports their suggested role in hormonal and mechano-sensitive signalling., Paxillin-GEF-H1-p42/44-MAPK module as a regulator of pathological mechanotransduction., MELK promotes cell migration and invasion via the FAK/Paxillin pathway, and plays an important role in the occurrence and development of gastric cancer., High PXN expression is associated with oral cavity squamous cell carcinoma., Through HDAC6-dependent regulation of the microtubule cytoskeleton, paxillin regulates both Golgi organelle integrity and polarized cell invasion., This chapter outlines recent advances in understanding how paxillin regulates both steroid and growth factor signaling, focusing on the conserved nature of its actions from a frog germ cell to a human cancer cell., MEKK2 induces paxillin ubiquitylation in breast cancer cells and this function requires both paxillin LD1 motif and MEKK2 kinase activity., Suggest paxillin up-regulation and phosphorylation as an important mechanism of vascular remodelling underlying pulmonary hypertension., Bcl-2 stabilization by paxillin confers 5-fluorouracil resistance in colorectal cancer., During early cell spreading, DLC1 is preferentially localized at the inner/mature adhesions whereas phosphorylated paxillin occupies the outer/nascent focal adhesions. In addition, DLC1 downregulates paxillin turnover, There was a concomitant decrease in the phosphorylation of focal adhesion kinase and paxillin, indicating that DPP9 knockdown or enzyme inhibition suppressed the associated adhesion signaling pathway, causing impaired cell movement., LPS-induced paxillin phosphorylation at Y31 and Y118 was mediated by c-Abl tyrosine kinase, In colorectal cancers PXN was positively correlated with Bcl-2, pBcl-2-S87, and MMP2 expression. PXN promotes Bcl-2 phosphorylation at Serine 87 via ERK activation, increases xenograft tumor formation, and associates with poor patient outcome., findings reveal a novel mechanism by which PTEN inhibits the progression of colon cancer by inhibiting paxillin expression downstream of PI3K/AKT/NF-kappaB pathway, these data suggested that miR-145 plays a pivotal role in colon cancer through inhibiting cell proliferation migration and invasion, and miR-145 may serve as a tumor suppressor by targeting paxillin gene., Paxillin was expressed at significantly higher levels in colorectal cancer tissues and might serve as a potential prognostic indicator in patients with colorectal cancer, Fascin-1 and paxillin were expressed in 58% and 43% of infiltrating duct carcinoma cases. There was a significant correlation between fascin-1 and paxillin expression and tumor grade, clinical stage, lymph-node metastasis grade, and HER2 expression., These findings suggest that PXN expression has potential use as a novel biomarker of laryngeal squamous cell carcinoma patients and may serve as an independent predictive factor for prognosis., Results showed that the positive rate of PXN was significantly higher in the colorectal adenocarcinoma samples and correlated with TNM stage, distant metastasis and recurrence additionally to cetuximab resistance., Data suggest that, in colonic/prostatic neoplasm cells, increased expression of NDRG1 decreases activating phosphorylation of FAK and paxillin; silencing/inhibition of NDRG1 results in opposite effect and inhibits neoplasm cell migration/adhesion., Mode of Action of Functionally Important Regions in the Intrinsically Disordered Paxillin, Bit1 may be an important regulator in cell growth, apoptosis, migration and invasion of esophageal squamous cell carcinoma via targeting FAK-paxillin pathway., blockade of GD3-mediated growth signaling pathways by siRNAs might be a novel and promising therapeutic strategy against malignant melanomas, provided signaling molecules such as p130Cas and paxillin are significantly expressed in individual cases.,
SP_COMMENT function:Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion)., PTM:Phosphorylated on tyrosine residues during integrin-mediated cell adhesion, embryonic development, fibroblast transformation and following stimulation of cells by mitogens., similarity:Belongs to the paxillin family., similarity:Contains 3 LIM zinc-binding domains., similarity:Contains 4 LIM zinc-binding domains., subunit:Binds in vitro to vinculin as well as to the SH3 domain of c-SRC and, when tyrosine phosphorylated, to the SH2 domain of V-CRK. Isoform beta binds to focal adhesion kinase but weakly to vinculin. Isoform gamma binds to vinculin but only weakly to focal adhesion kinase. Interacts with GIT1, NUDT16L1/SDOS, PARVA and TGFB1I1. Component of cytoplasmic complexes, which also contain GIT1, ARHGEF6 and PAK1 (By similarity). Binds ASAP2. Interacts with unphosphorylated ITGA4. Interacts with RNF5.,