KinaseVinculinProteinsReceptor tyrosinProteinLocalizationRegulatesIntegrinComplexesTurnoverResiduesCytoskeletonOverexpressionCoprecipitationFibersMotilityMyosinIntegrinsSignaling moleculesOccursSuppressesProtrusionRhoAMediatesInteractionsExtracellularMolecularFormationTransientMutantStructuresExpressionSitesShownCell-cellHumanHighlyActivationProcessResultTypes
Kinase15
- 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)
- We also know that the binding of paxillin to focal adhesion kinase (FAK) is critical for directing paxillin function. (wikipedia.org)
- p21-activated kinase 4 (PAK4), a specific effector of the Rho GTPase Cdc42, is activated by HGF, and we have previously shown that activated PAK4 induces a loss of both actin stress fibres and focal adhesions. (silverchair.com)
- The Rho kinase inhibitor Y27632 completely blocks acid-induced stress fiber formation and the increases in apical membrane NHE3 abundance and activity, but it has no effect on acid-induced tyrosine phosphorylation of p125 FAK or paxillin. (elsevierpure.com)
- Acid-induced tyrosine phosphorylation of the focal adhesion proteins p125 FAK and paxillin is not Rho kinase dependent. (elsevierpure.com)
- FAK is a non-receptor tyrosine kinase involved in a wide variety of biological processes and crucial for embryonic development. (biologists.com)
- FAK is composed of three major domains, the N-terminal FERM (4.1-band, ezrin, radixin, moesin) domain, followed by the central catalytic kinase domain and the C-terminal focal adhesion targeting (FAT) domain. (biologists.com)
- 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)
- Both vinY822F and vin −/− cells exhibit increased interaction between paxillin and focal adhesion kinase (FAK) and increased paxillin and FAK phosphorylation. (rupress.org)
- We have identified a novel pathway that directs Lyn/Src family tyrosine kinase signals to the invadopodia to regulate sarcoma cell invasion via the molecule AFAP-1-like-1 (AFAP1L1), a new member of the AFAP (actin filament-associated protein) family. (nature.com)
- AFAP1L1 intersects several invadopodia pathway components through its multiple domains and motifs, including the following (i) pleckstrin homology domains that bind phospholipids generated at the plasma membrane by phosphoinositide 3-kinase, (ii) a direct filamentous-actin binding domain and (iii) phospho-tyrosine motifs (pY136 and pY566) that specifically bind Vav2 and Nck2 SH2 domains, respectively. (nature.com)
- Through its interaction with Vav2, AFAP1L1 regulates Rac activity and downstream control of PAK1/2/3 (p21-activated kinases) phosphorylation of myosin light chain (MLC) kinase and MLC2. (nature.com)
- These data define a novel pathway that directs Lyn/Src family tyrosine kinase signals to sarcoma cell invadopodia through specific recruitment of Vav2 and Nck2 to phosphorylated AFAP1L1, to control cell migration and invasion. (nature.com)
- 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)
- Focal adhesion kinase (FAK) and steroid receptor coactivator (c-Src) are signaling proteins that regulate cytoskeletal dynamics and cell motility by influencing actin polymerization and focal adhesion turn-over [ 11 , 12 ]. (biomedcentral.com)
Vinculin14
- 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)
- 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)
- A vinculin fragment (amino acids 811-1066) containing the paxillin binding site restored apoptosis and suppressed ERK activity in vin −/− cells. (rupress.org)
- Thus, vinculin regulates survival and motility via ERK by controlling the accessibility of paxillin for FAK interaction. (rupress.org)
- Although focal adhesions are similar, in terms of molecular composition, to nascent adhesions and focal complexes, several adhesion proteins appear to change as focal adhesions evolve in response to tension, e.g., zyxin and vinculin . (cellmigration.org)
- Vinculin expression in focal adhesions upon EL treatment was determined by immunocytochemistry. (biomedcentral.com)
- Mechanisms and Functions of Vinculin Interactions with Phospholipids at Cell Adhesion Sites. (univ-paris5.fr)
- A plastic relationship between vinculin-mediated tension and adhesion complex area defines adhesion size and lifetime. (univ-paris5.fr)
- Lipid binding promotes oligomerization and focal adhesion activity of vinculin. (univ-paris5.fr)
- Vinculin phosphorylation differentially regulates mechanotransduction at cell-cell and cell-matrix adhesions. (univ-paris5.fr)
- Identification of an actin binding surface on vinculin that mediates mechanical cell and focal adhesion properties. (univ-paris5.fr)
- Deletion of the cell adhesion adaptor protein vinculin disturbs the localization of GFAP in Bergmann glial cells. (univ-paris5.fr)
- RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover. (univ-paris5.fr)
- Vinculin regulates the recruitment and release of core focal adhesion proteins in a force-dependent manner. (univ-paris5.fr)
Proteins4
- 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)
- Formation of stress fibers is associated with acid-induced tyrosine phosphorylation and increases in protein abundance of two focal adhesion proteins, p125 FAK and paxillin. (elsevierpure.com)
- Adhesion complexes (i.e., focal adhesions and focal complexes) and cell-cell contacts are specialized structures that harbor a large number of cytoskeletal proteins and one of the highest concentrations of signaling molecules in cells ( Ruoslahti and Obrink, 1996 ). (rupress.org)
- Our data suggest that EL suppresses lung cancer cell motility and invasion by altering FAK activity and subsequent activation of downstream proteins needed for focal adhesion formation and cytoskeletal rearrangement. (biomedcentral.com)
Receptor tyrosin3
- RESULTS Identification of a 95-kDa Tyrosine Phosphorylated Nck-binding Protein The SH3-SH3-SH3-SH2 adaptor protein Nck is a major downstream mediator of extracellular matrix and growth element receptor signaling to the cytoskeleton through its ability to associate with receptor tyrosine kinases PAK and the WASP/WAVE complex (Buday and indicated like a Box-and-Whiskers Storyline (Number 10B). (healthyguide.info)
- My laboratory is focused on understanding mechanisms of resistance to molecular targeting agents directed against receptor tyrosine kinases. (wisc.edu)
- Monoclonal antibody therapy has been developed over the past 30 years to target receptor tyrosine kinases (RTKs), which sit on the outer membrane of cancerous cells. (wisc.edu)
Protein13
- 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)
- these serve as binding sites for the protein tyrosine phosphatase-PEST, tubulin and serves as the targeting motif for focal adhesions. (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 N-terminal region of paxillin is rich in protein-protein interaction sites. (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)
- 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)
- We show that the FERM domain has a role in the recruitment of FAK on focal adhesions and controls the dynamics of the protein on these complexes. (biologists.com)
- Therefore abrogation of appropriate temporal-spatial rules of PKL profoundly impairs normal cell adhesion dynamics consistent with a critical part for this protein Panobinostat and its binding partners. (healthyguide.info)
- The related protein GIT1 is definitely tyrosine phosphorylated inside a Src-dependent manner (Bagrodia (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-02-0131) in July. (healthyguide.info)
- 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)
- In addition, FTS treatment resulted in decreased Ras protein ranges, indicating that Ras signaling is important for NO to improve Ets 1 phosphorylation. (checkpointinhibitor.com)
Localization5
- Similarly, paxillin was shown to have altered localization in cardiomyocytes from transgenic mice expressing a constitutively-active rac1. (wikipedia.org)
- 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)
- The absence of either FAK or Src-family kinases prevents PKL phosphorylation and suppresses localization of PKL Panobinostat but not GIT1 to focal adhesions after Rac activation. (healthyguide.info)
- Manifestation of Panobinostat an triggered FAK mutant in the absence of Src-family kinases partially restores PKL localization suggesting that Src activation of FAK is required for PKL phosphorylation and localization. (healthyguide.info)
- 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)
Regulates1
- 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)
Integrin2
- Both of these sites may be involved in Crk binding to paxillin during integrin-mediated cell adhesion. (ecmbio.com)
- Similarly, depletion of either Rasip1 or Arhgap29 in cultured ECs blocks in vitro lumen formation, fundamentally alters the cytoskeleton, and reduces integrin-dependent adhesion to ECM . (xenbase.org)
Complexes3
- Rasipl null angioblasts fail to properly localize the polarity determinant Par3 and display defective cell polarity, resulting in mislocalized junctional complexes and loss of adhesion to extracellular matrix ( ECM ). (xenbase.org)
- other signaling adaptors are also recruited to these complexes, including FAK and paxillin. (cellmigration.org)
- Focal complexes are adhesions in the early stages of maturation. (cellmigration.org)
Turnover4
- Moreover, these cells have a concomitant reduction in cell-adhesion turnover rates. (silverchair.com)
- Expression of FF blocks focal adhesion turnover and, unlike FRNK, acts as a dominant negative in vivo . (biologists.com)
- These signals are also required for the dissolution of some adhesions (turnover) as the cell advances. (cellmigration.org)
- Like nascent adhesions, they also tend to either disassemble (turnover) or grow and elongate into focal adhesions. (cellmigration.org)
Residues1
- 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)
Cytoskeleton1
- Migration and invasion require coordinated reorganisation of the actin cytoskeleton and regulation of cell-adhesion dynamics. (silverchair.com)
Overexpression2
- In a mouse model of tropomodulin overexpression, paxillin distribution was revamped coordinate with increased phosphorylation and cleavage of paxillin. (wikipedia.org)
- 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)
Coprecipitation2
- 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)
- 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)
Fibers3
- We found that mutation of Tyr31/118 caused enhanced activation of RhoA and premature formation of stress fibers with substantial loss of efficient membrane spreading and ruffling in adhesion and migration of NMuMG cells. (silverchair.com)
- EL treatment reduced the density and number of F-actin fibers in lung cancer cell lines, and reduced the number and size of focal adhesions. (biomedcentral.com)
- The best-characterized molecules are Rho, which controls the stress fibers and focal adhesion formation, and Rac and Cdc42, which regulate membrane ruffling, and filopodium formation, respectively. (biomedcentral.com)
Motility2
- These adhesions are usually physically linked to large, readily visualized actomyosin bundles [13] , and their appearance correlates inversely with motility, such that they are conspicuously absent in cells migrating within a three-dimensional (3D) substrate. (cellmigration.org)
- EL decreased phosphorylation of FAK and its downstream targets, Src, paxillin, and decreased mRNA expression of cell motility-related genes, RhoA, Rac1, and Cdc42 in lung cancer cells. (biomedcentral.com)
Myosin3
- These adhesions generate signals that activate Rac, promoting actin polymerization and preventing myosin II engagement in the lamellipodium. (cellmigration.org)
- Rho activation is thought to generate focal adhesions and actin bundling due to increased myosin II activity. (cellmigration.org)
- They are larger than nascent adhesions, depend on myosin II for their formation and maintenance, and reside at the boundary of the lamellum and lamellipodium [10] , [11] . (cellmigration.org)
Integrins1
- Tyrosine phosphorylation of paxillin occurs in response to growth factors, neuropeptides, and integrins. (ecmbio.com)
Signaling molecules1
- These sites may provide docking motifs for recruitment of other signaling molecules to focal adhesions. (ecmbio.com)
Occurs2
- 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)
- Phosphorylation of paxillin occurs at both tyrosine and serine sites. (ecmbio.com)
Suppresses1
- 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)
Protrusion1
- 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)
RhoA2
- 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)
- Whereas the formation of focal adhesions requires actomyosin-mediated contractile force mediated by RhoA , podosome formation is stimulated by a local loss of contractility and the recruitment of negative regulators of RhoA, such as p190RhoGAP [16] . (cellmigration.org)
Mediates1
- Cell-matrix adhesion is the best-studied form of adhesion that mediates cell migration, and is the focus of this outline. (cellmigration.org)
Interactions1
- This increase is shown to result from vinculin's modulation of paxillin-FAK interactions. (rupress.org)
Extracellular3
- 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)
- 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)
- Cell adhesion (the physical interaction of a cell with another cell or with the extracellular matrix (ECM)) is essential for cell migration and tissue integrity. (cellmigration.org)
Molecular2
- Human paxillin is 64.5 kDa in molecular weight and 591 amino acids in length. (wikipedia.org)
- Although their molecular composition is very similar to that of focal adhesions, their spatial distribution is radial, forming dot-like structures similar to 'suction cups' [14] . (cellmigration.org)
Formation2
- Paxillin is involved in focal adhesion formation during cell adhesion and migration. (ecmbio.com)
- Herbimycin A completely blocks acid-induced tyrosine phosphorylation of p125 FAK and paxillin but only partially blocks stress fiber formation and NHE3 activation. (elsevierpure.com)
Transient1
- Nascent adhesions are small and highly transient - either maturing or disassembling ('turning over') - and are therefore not easily observed in every cell type [6] , [7] . (cellmigration.org)
Mutant1
- Transfection with paxillin Y31FY118F dominant-negative mutant in these cells inhibits ERK activation and restores apoptosis. (rupress.org)
Structures1
- Nascent adhesions are the first observable adhesive structures, emerging within the lamellipodium. (cellmigration.org)
Expression2
- 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)
- We now report that DU145 human prostate cancer cells with reduced levels of PAK4 expression are unable to successfully migrate in response to HGF, have prominent actin stress fibres, and an increase in the size and number of focal adhesions. (silverchair.com)
Sites1
- The major sites of tyrosine phosphorylation include Tyr-31 and Tyr-118. (ecmbio.com)
Shown1
- Additional studies have shown that paxillin itself is phosphorylated, and this participates in hypertrophic signaling pathways in cardiomyocytes. (wikipedia.org)
Cell-cell1
- Cell-cell adhesion maintains epithelial tissues, supports functional contacts between specialized cells, and can facilitate directed migration (for example, radial glia can guide neuronal progenitor cells to specific layers of the brain). (cellmigration.org)
Human1
- This human sequence is highly conserved in rat and mouse paxillin. (ecmbio.com)
Highly1
- Owing to their highly localized nature, cell-matrix adhesions were initially called focal adhesions. (cellmigration.org)
Activation1
- Both cell adhesion and Rac activation stimulated PKL tyrosine phosphorylation. (healthyguide.info)
Process2
- 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)
- Scheme depicts the process of adhesion maturation. (cellmigration.org)
Result2
- EGF and DETANO resulted in Ets one phosphorylation, nevertheless, this signaling result was not observed within the pre sence of FTS. (checkpointinhibitor.com)
- Constant with all the Ets 1 phosphorylation success, FTS blocked the result of NO to improve Ets one transcriptional exercise, even though G 6976 had no result on luciferase exercise. (checkpointinhibitor.com)
Types1
- Over the years, several types of cell-matrix adhesion have been described. (cellmigration.org)