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PaxillinFocal Adhesion Kinase 2Focal AdhesionsFocal Adhesion Protein-Tyrosine KinasesFocal Adhesion Kinase 1TyrosineProtein-Tyrosine KinasesPhosphorylationCrk-Associated Substrate ProteinCell AdhesionActinsPhosphoproteinsCell Adhesion MoleculesPhosphotyrosineCytoskeletal ProteinsVinculinSignal TransductionCell MovementCytoskeletonsrc-Family KinasesCells, CulturedEnzyme ActivationCell LineIntegrinsActin CytoskeletonProtein Tyrosine PhosphatasesProtein BindingMolecular Sequence DataAmino Acid SequenceTissue AdhesionsIntercellular Adhesion Molecule-1ZyxinActin Depolymerizing FactorsFibronectinsProto-Oncogene Proteins pp60(c-src)TransfectionRetinoblastoma-Like Protein p130Talin3T3 CellsAntigens, CD29Adaptor Proteins, Signal Transducingsrc Homology DomainsEnzyme InhibitorsSerineVanadatesFibroblastsProtein-Serine-Threonine KinasesIntracellular Signaling Peptides and ProteinsPrecipitin TestsBlotting, WesternProtein Structure, TertiaryRecombinant Fusion ProteinsVascular Cell Adhesion Molecule-1ActininProto-Oncogene ProteinsProteinsMutationStress FibersPhosphatidylinositol 3-KinasesCell Line, Tumorrho GTP-Binding ProteinsMicroscopy, FluorescenceCytochalasin DExtracellular MatrixProto-Oncogene Proteins c-crkrhoA GTP-Binding ProteinProto-Oncogene Proteins c-fynProtein Kinase CImmunoblottingBinding SitesPseudopodiaRecombinant ProteinsGenisteinMitogen-Activated Protein KinasesKineticsTumor Cells, CulturedLIM Domain ProteinsProtein KinasesProtein Tyrosine Phosphatase, Non-Receptor Type 11Bacterial AdhesionModels, BiologicalMicrofilament ProteinsEndothelium, VascularCell MembraneMembrane ProteinsImmunoprecipitationMitogen-Activated Protein Kinase 1Time FactorsCOS CellsCalcium-Calmodulin-Dependent Protein KinasesGTPase-Activating ProteinsProto-Oncogene Proteins c-aktCalciumPhospholipase C gammaProtein TransportPhosphoserineRNA, Small InterferingCadherinsCricetinaerac1 GTP-Binding Protein
CytoskeletonKinaseProteinsNascent adhesionsPromoting actin polymerizationVinculinRegulatesComplexesFibersFilamentous-actinMyosinTurnoverSignaling moleculesRecruitmentMaturationLamellipodiumRegulationElongationExtracellularMotilityIntegrinsMigrationStructuresRhoAInteractionsOccursLipidInitiallyMolecularFormationCellsAminoSitesResponse
Cytoskeleton5
  • Migration and invasion require coordinated reorganisation of the actin cytoskeleton and regulation of cell-adhesion dynamics. (silverchair.com)
  • They are sites of convergence between the actin cytoskeleton and ECM fibrils. (cellmigration.org)
  • One of the main functions of FAs is to physically connect the cellular actin cytoskeleton to ECM, therefore sensing, integrating, and transducing extracellular signaling. (life-science-alliance.org)
  • A common theme of these processes is a dynamic reorganization of actin cytoskeleton which has now emerged as a major switch control mainly carried out by Rho and Rac GTPase subfamilies, playing an acknowledged role in adaptation of cell motility to the microenvironment. (biomedcentral.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)
Kinase13
  • 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)
  • 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)
  • 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)
  • Both vinY822F and vin −/− cells exhibit increased interaction between paxillin and focal adhesion kinase (FAK) and increased paxillin and FAK phosphorylation. (rupress.org)
  • 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)
  • Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). (uci.edu)
Proteins8
Nascent adhesions6
  • Nascent adhesions are the first observable adhesive structures, emerging within the lamellipodium. (cellmigration.org)
  • 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)
  • 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)
  • Like nascent adhesions, they also tend to either disassemble (turnover) or grow and elongate into focal adhesions. (cellmigration.org)
  • Newly formed nascent adhesions gradually grow and change their protein composition to mature into FAs. (life-science-alliance.org)
  • From left: Panel 1 shows formation of nascent adhesions at the cell periphery. (mechanobio.info)
Promoting actin polymerization1
  • These adhesions generate signals that activate Rac, promoting actin polymerization and preventing myosin II engagement in the lamellipodium. (cellmigration.org)
Vinculin12
Regulates3
  • Here we showed that in migrating MDA-MB-231 cells Rab40c regulates focal adhesion's number, size, and distribution. (life-science-alliance.org)
  • Thus, we propose a model where Rab40c/CRL5 regulates ANKRD28 ubiquitylation and degradation, leading to a decrease in PP6 activity, which ultimately affects FAK and Hippo pathway signaling to alter focal adhesion dynamics. (life-science-alliance.org)
  • FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. (uci.edu)
Complexes5
  • AFAP1L1 interaction with Nck2 recruits actin-nucleating complexes. (nature.com)
  • 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)
  • 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)
  • 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)
Fibers4
  • 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)
  • 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)
  • 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)
  • In panel 2, some adhesions attach to stress fibers and grow in size while some disassemble (yellow with dotted outline) at the lamellipodium-lamellum boundary. (mechanobio.info)
Filamentous-actin2
  • Significantly, in osteosarcoma cell lines, knockdown of AFAP1L1 inhibits phosphorylated MLC2 recruitment to filamentous-actin structures, disrupts invadopodia formation, cell attachment, migration and invasion. (nature.com)
  • Changes in filamentous actin (F-actin) fiber density and length in EL-treated cells were determined using phalloidin-conjugated rhodamine dye and fluorescent microscopy. (biomedcentral.com)
Myosin1
Turnover3
  • Moreover, these cells have a concomitant reduction in cell-adhesion turnover rates. (silverchair.com)
  • These signals are also required for the dissolution of some adhesions (turnover) as the cell advances. (cellmigration.org)
  • Expression of FF blocks focal adhesion turnover and, unlike FRNK, acts as a dominant negative in vivo . (biologists.com)
Signaling molecules1
Recruitment1
  • 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)
Maturation3
  • Scheme depicts the process of adhesion maturation. (cellmigration.org)
  • Fibrillar adhesions represent an extreme in the maturation of adhesions and are not generally seen in migrating cells. (cellmigration.org)
  • The protrusions of the cell edge are shown as green arrows corresponding to points of adhesion maturation (panels 3 and 4). (mechanobio.info)
Lamellipodium2
  • Focal adhesions act as molecular clutches that provide grip to the substrate for the lamellipodium to protrude forward during motility. (mechanobio.info)
  • At the lamellipodium-lamellum interface, unstable adhesions disappear and stable ones start to elongate in a centripetal fashion along the direction of actin retrograde flow. (mechanobio.info)
Regulation1
Elongation2
  • Actin, microtubules, and vimentin intermediate filaments cooperate for elongation of invadopodia. (nature.com)
  • The elongation occurs along a template of bundled actin [7] . (cellmigration.org)
Extracellular1
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)
Integrins1
Migration6
  • 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)
  • Cell-matrix adhesion is the best-studied form of adhesion that mediates cell migration, and is the focus of this outline. (cellmigration.org)
  • 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)
  • 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)
  • With nascent adhesion formation at the leading edge, the FAs at the cell rear need to be disassembled to promote rear end retraction and efficient cell migration. (life-science-alliance.org)
  • Paxillin is involved in focal adhesion formation during cell adhesion and migration. (ecmbio.com)
Structures1
  • 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)
RhoA1
  • 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)
Interactions1
  • This increase is shown to result from vinculin's modulation of paxillin-FAK interactions. (rupress.org)
Occurs1
Lipid2
  • Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control. (uci.edu)
  • We detected phosphorylation on S155 and identified S155 as a functionally important site for lipid metabolism. (uci.edu)
Initially1
Molecular1
  • 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)
Formation4
Cells6
  • 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)
  • Podosomes are ring-shaped adhesions often found in fast-moving cells, such as macrophages. (cellmigration.org)
  • Transfection with paxillin Y31FY118F dominant-negative mutant in these cells inhibits ERK activation and restores apoptosis. (rupress.org)
  • On the cover: Human induced pluripotent stem cell-derived neuroepithelial-like stem cells stained for actin (green) and DNA (blue). (5dok.org)
  • We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. (uci.edu)
  • Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation. (uci.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)
Sites2
Response1
  • Furthermore, rNLRC3 significantly inhibited the activation of NF-κB by reducing phosphorylation and nuclear import of p65 in response to P. multocida infection. (bvsalud.org)