AnatomyChemicals and DrugsPhenomena and Processes
PaxillinCytoskeletal ProteinsFocal Adhesion Protein-Tyrosine KinasesFocal Adhesion Kinase 1PhosphoproteinsFocal AdhesionsVinculinProtein-Tyrosine KinasesCell Adhesion MoleculesTyrosinePhosphorylationCrk-Associated Substrate ProteinCell AdhesionProtein Tyrosine Phosphatase, Non-Receptor Type 12Proto-Oncogene Proteins c-crkLIM Domain ProteinsFocal Adhesion Kinase 2Cell MovementCytoskeletonRetinoblastoma-Like Protein p130PhosphotyrosineActinsTalinActininCytochalasin DSignal TransductionZyxinProtein Bindingsrc-Family KinasesIntegrinsIntegrin alpha4
Phosphorylation of paxillinFocal adhesionsTarget paxillin to focalPyk2Adaptor proteinAntibodyHighly conservedCytoskeletal proteinsProteinRegulatesOverexpressionCoprecipitationMoleculeSignaling pathwayProteinsMolecularRhoABindsAdhesionApoptosisInhibitsCytoskeletonLocalizationInhibitorsCardiomyopathyMutantInvasionAminoComplexesFunctionCellsMouseActivityIncreaseShown
Phosphorylation of paxillin4
Focal adhesions8
  • Paxillin is expressed at focal adhesions of non-striated cells and at costameres of striated muscle cells, and it functions to adhere cells to the extracellular matrix. (wikipedia.org)
  • Paxillin is a signal transduction adaptor protein discovered in 1990 in the laboratory of Keith Burridge The C-terminal region of paxillin contains four LIM domains that target paxillin to focal adhesions. (wikipedia.org)
  • The current working model of costamerogenesis is that in cultured, undifferentiated myoblasts, alpha-5 integrin, vinculin and paxillin are in complex and located primarily at focal adhesions. (wikipedia.org)
  • These complexes, which are associated with lamellipodia and filopodia, contain vinculin, paxillin, and focal adhesion kinase, but are distinct from and formed independently of rho-induced focal adhesions. (nih.gov)
  • The ArfGAP paxillin kinase linker (PKL)/G protein-coupled receptor kinase-interacting protein (GIT)2 continues to be implicated in regulating cell spreading and motility through its transient recruitment of the p21-activated kinase (PAK) to focal adhesions. (healthyguide.info)
  • PKL is definitely phosphorylated on tyrosine residues 286/392/592 by Src and/or FAK and these sites are required for PKL localization to focal adhesions and for paxillin binding. (healthyguide.info)
  • Overexpression of the nonphosphorylated GFP-PKL Triple YF mutant stimulates cell distributing and protrusiveness much like overexpression of a paxillin mutant that does not bind PKL suggesting that failure to recruit PKL to focal adhesions interferes with normal cell distributing and motility. (healthyguide.info)
  • This photoactivation localization microscopy (PALM) image of tdEos-vinculin (red) and Dronpa-paxillin (green) illustrates that vinculin and paxillin are segregated into interlocking microdomains within focal adhesions. (ucsd.edu)
Target paxillin to focal1
  • Paxillin?s C- terminal region consist of four LIM domains that interacts with cytoplasmic tail of beta-integrin to target paxillin to focal adhesion. (biogenex.com)
Pyk29
  • Focal adhesion targeting (FAT) domains target the non-receptor tyrosine kinases FAK and Pyk2 to cellular focal adhesion areas, where the signaling molecule paxillin is also located. (rcsb.org)
  • Here, we report the crystal structures of the Pyk2 FAT domain alone or in complex with paxillin LD4 peptides. (rcsb.org)
  • In the LD4-bound FAT complex, two paxillin LD4 peptides interact with two opposite sides of Pyk2-FAT, at the surfaces of the alpha1alpha4 and alpha2alpha3 helices of each FAT molecule. (rcsb.org)
  • We also demonstrate that, while paxillin is phosphorylated by Pyk2, complex formation between Pyk2 and paxillin does not depend on Pyk2 tyrosine kinase activity. (rcsb.org)
  • These experiments reveal the structural basis underlying the selectivity of paxillin LD4 binding to the Pyk2 FAT domain and provide insights about the molecular details which influence the different behavior of these two closely-related kinases. (rcsb.org)
  • However, cytochalasin D treatment had no effect on NA-induced and ET-induced phosphorylation of either PYK2 or paxillin but did prevent their association with the TritonX-100 insoluble membrane compartment. (manchester.ac.uk)
  • These results show that in mesenteric arteries an intact cytoskeleton and force development are not prerequisites for G-protein-coupled receptor-induced activation of PYK2 and paxillin, by tyrosine phosphorylation, in vascular tissue, but are necessary for the translocation of PYK2 and paxillin to the membrane. (manchester.ac.uk)
  • Ohanian, V, Gatfield, K & Ohanian, J 2005, ' Role of the actin cytoskeleton in G-protein-coupled receptor activation of PYK2 and paxillin in vascular smooth muscle ', Hypertension , vol. 46, no. 1, pp. 93-99. (manchester.ac.uk)
  • Podosomes are structurally divided into a core, which mainly contains proteins involved in actin polymerization (such as WASP, the Arp2/3 complex and cortactin ), and a surrounding ring populated by integrin receptors and adhesion proteins (for example, paxillin and focal adhesion kinase (FAK/Pyk2) ) [15] . (cellmigration.org)
Adaptor protein1
Antibody1
  • This antibody detects a 72kDa* protein corresponding to the molecular mass of phosphorylated paxillin on SDS-PAGE immunoblots of pervanadate treated A431 cells, but not in A431 control cells. (ecmbio.com)
Highly conserved2
  • The N-terminal region of paxillin has five highly conserved leucine-rich sequences termed LD motifs, which mediate several interactions, including that with pp125FAK and vinculin. (wikipedia.org)
  • This human sequence is highly conserved in rat and mouse paxillin. (ecmbio.com)
Cytoskeletal proteins1
  • Paxillin contains LD motifs, LIM domains, and an SH3- and SH2-binding domain that participate in a variety of protein-protein interactions with kinases, GTPase-activating proteins, and cytoskeletal proteins. (ecmbio.com)
Protein9
  • Paxillin is a protein that in humans is encoded by the PXN gene. (wikipedia.org)
  • Mutations in PXN as well as abnormal expression of paxillin protein has been implicated in the progression of various cancers. (wikipedia.org)
  • The N-terminal region of paxillin is rich in protein-protein interaction sites. (wikipedia.org)
  • The proteins that bind to paxillin are diverse and include protein tyrosine kinases, such as Src and focal adhesion kinase (FAK), structural proteins, such as vinculin and actopaxin, and regulators of actin organization, such as COOL/PIX and PKL/GIT. (wikipedia.org)
  • Paxillin is tyrosine-phosphorylated by FAK and Src upon integrin engagement or growth factor stimulation, creating binding sites for the adapter protein Crk. (wikipedia.org)
  • Treatment of cardiomyocytes with the hypertrophic agonist, phenylephrine stimulated a rapid increase in tyrosine phosphorylation paxillin, which was mediated by protein tyrosine kinases. (wikipedia.org)
  • Paxillin is a multidomain cytoskeletal protein with a role in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). (biogenex.com)
  • Paxillin, an integrin-assembly protein, has four major tyrosine phosphorylation sites, and the phosphorylation of Tyr31 and Tyr118 correlates with cell adhesion and migration. (silverchair.com)
  • Vertebrate paxillin, a cytoskeletal focal adhesion protein. (embl.de)
Regulates4
  • The phosphorylation of FAK at serine-910 regulates the interaction of FAK with paxillin, and controls the stability of paxillin at costameres in cardiomyocytes, with phosphorylation reducing the half-life of paxillin. (wikipedia.org)
  • Thus, vinculin regulates survival and motility via ERK by controlling the accessibility of paxillin for FAK interaction. (rupress.org)
  • Dubois, F., Alpha, K. and Turner, C.E. (2017) Paxillin Regulates Cell Polarization and Anterograde Vesicle Trafficking during Cell Migration. (upstate.edu)
  • A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability. (mpg.de)
Overexpression1
Coprecipitation2
  • Phosphorylated Tyr31/118 was found to bind to two src homology (SH)2 domains of p120RasGAP, with coprecipitation of endogenous paxillin with p120RasGAP. (silverchair.com)
  • For paxillin coprecipitation transiently transfected Chinese hamster ovary (CHO).K1 or HEK293A cells were replated about 10 μg/ml fibronectin for 60 min before control. (healthyguide.info)
Molecule1
  • Our results highlight paxillin as a core molecule in substrate modulus-controlled morphogenesis and define a mechanism whereby neuronal cells respond to environments exhibiting varying mechanical properties. (elifesciences.org)
Signaling pathway1
  • The active phosphorylated form of FAK/Paxillin signaling pathway proteins and active form of RhoA were decreased. (ntnu.edu.tw)
Proteins1
  • We are particularly interested in characterizing the function of the molecular scaffold/adapter proteins Paxillin and it's close relative Hic-5 during tumor cell migration and invasion. (upstate.edu)
Molecular1
RhoA3
  • By contrast, on rigid substrates, cells develop extensive adhesions, increase RhoA activity and sequester paxillin from the endocytic machinery, thereby delaying neurite initiation. (elifesciences.org)
  • We found that Tyr31/118-phosphorylated paxillin competes with p190RhoGAP for binding to p120RasGAP, and provides evidence that p190RhoGAP freed from p120RasGAP efficiently suppresses RhoA activity during cell adhesion. (silverchair.com)
  • We conclude that Tyr31/118-phosphorylated paxillin serves as a template for the localized suppression of RhoA activity and is necessary for efficient membrane spreading and ruffling in adhesion and migration of NMuMG cells. (silverchair.com)
Binds2
  • The proline-rich region of paxillin specifically binds to the second SH3 domain of ponsin, which occurs after the onset of the myogenic differentiation and with expression restricted to costameres. (wikipedia.org)
  • On soft substrates, most paxillin binds to endocytic factors and facilitates vesicle invagination, elevating neuritogenic Rac1 activity and expression of genes encoding the endocytic machinery. (elifesciences.org)
Adhesion8
  • In striated muscle cells, paxillin is important in costamerogenesis, or the formation of costameres, which are specialized focal adhesion-like structures in muscle cells that tether Z-disc structures across the sarcolemma to the extracellular matrix. (wikipedia.org)
  • We also know that the binding of paxillin to focal adhesion kinase (FAK) is critical for directing paxillin function. (wikipedia.org)
  • Using hydrogel cultures, pharmacologic inhibition, and genetic approaches, we reveal that paxillin-linked endocytosis and adhesion are components of a bistable switch controlling neurite initiation in a substrate modulus-dependent manner. (elifesciences.org)
  • Both vinY822F and vin −/− cells exhibit increased interaction between paxillin and focal adhesion kinase (FAK) and increased paxillin and FAK phosphorylation. (rupress.org)
  • Paxillin is involved in focal adhesion formation during cell adhesion and migration. (ecmbio.com)
  • Both of these sites may be involved in Crk binding to paxillin during integrin-mediated cell adhesion. (ecmbio.com)
  • A) Normal MEF cells were transfected and plated on 5 μg/ml fibronectin for 180 min followed by acquisition of time-lapse images every … DISCUSSION We have recognized Src/FAK- and Rac-dependent phosphorylation of the ArfGAP PKL and identified that phosphorylation is required for PKL focal adhesion localization paxillin binding and normal cell adhesion dynamics. (healthyguide.info)
  • Turner, C.E., (2000) Paxillin and focal adhesion signaling. (upstate.edu)
Apoptosis2
  • A vinculin fragment (amino acids 811-1066) containing the paxillin binding site restored apoptosis and suppressed ERK activity in vin −/− cells. (rupress.org)
  • Transfection with paxillin Y31FY118F dominant-negative mutant in these cells inhibits ERK activation and restores apoptosis. (rupress.org)
Inhibits1
  • In addition, SK228 inhibits cancer cell invasion via FAK/Paxillin disruption at noncytotoxic doses. (ntnu.edu.tw)
Cytoskeleton1
Localization1
  • Similarly, paxillin was shown to have altered localization in cardiomyocytes from transgenic mice expressing a constitutively-active rac1. (wikipedia.org)
Inhibitors1
Cardiomyopathy4
  • The structural reorganization of paxillin in cardiomyocytes has also been detected in mouse models of dilated cardiomyopathy. (wikipedia.org)
  • These data show that alterations in costameric organization, in part via paxillin redistribution, may be a pathogenic mechanism in dilated cardiomyopathy. (wikipedia.org)
  • In addition, in mice subjected to pressure overload-induced cardiac hypertrophy, inducing hypertrophic cardiomyopathy, paxillin expression levels increased, suggesting a role for paxillin in both types of cardiomyopathy. (wikipedia.org)
  • Corroborating results showed altered localizations of src in dilated cardiomyopathy and paxillin in both cardiomyopathic phenotypes. (jci.org)
Mutant1
  • Based on the observation that SADDAN-FGFR3 causes alterations in cell morphology, we analyzed whether this mutant could affect cytoskeletal organization through paxillin (PXN) function. (univr.it)
Invasion1
  • C.E. (2011) Paxillin and Hic-5 cooperate to regulate breast cancer cell plasticity, invasion and metastasis. (upstate.edu)
Amino1
  • Clone M102 was generated from phospho-Paxillin (Tyr-31) synthetic peptide (coupled to KLH) corresponding to amino acid residues around tyrosine 31 of human paxillin. (ecmbio.com)
Complexes1
Function1
  • While the precise functions of paxillin in this process are still being unveiled, studies investigating binding partners of paxillin have provided mechanistic understanding of its function. (wikipedia.org)
Cells4
  • Epithelial cells of various tissues, neuronal cells and mesenchymal derived cells express Paxillin. (biogenex.com)
  • GFP-Paxillin WT-expressing cells functioned basically the same as GFP control cells. (healthyguide.info)
  • Notably both GFP-PKL Triple YF and GFP-PaxillinΔLD4-expressing cells displayed higher fluctuations in protrusion area changes prominently indicated from the span (minimum amount and maximum value) of the "whiskers. (healthyguide.info)
  • Manifestation of GFP-PKL TripleYF raises cell protrusiveness much like cells expressing paxillin ΔLD4. (healthyguide.info)
Mouse1
Activity1
Increase1
  • This increase is shown to result from vinculin's modulation of paxillin-FAK interactions. (rupress.org)
Shown1
  • Additional studies have shown that paxillin itself is phosphorylated, and this participates in hypertrophic signaling pathways in cardiomyocytes. (wikipedia.org)