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PaxillinFocal AdhesionsFocal Adhesion Kinase 2Focal Adhesion Protein-Tyrosine KinasesFocal Adhesion Kinase 1TyrosineProtein-Tyrosine KinasesCell AdhesionPhosphorylationCrk-Associated Substrate ProteinCell Adhesion MoleculesPhosphoproteinsVinculinCytoskeletal ProteinsPhosphotyrosineSignal TransductionCell MovementIntegrinssrc-Family KinasesTissue AdhesionsCells, CulturedCytoskeletonEnzyme ActivationCell LineIntercellular Adhesion Molecule-1ActinsZyxinProtein Tyrosine PhosphatasesFibronectinsTalinProtein BindingAntigens, CD29Molecular Sequence DataAmino Acid SequenceRetinoblastoma-Like Protein p130Vascular Cell Adhesion Molecule-1Proto-Oncogene Proteins pp60(c-src)Transfection3T3 CellsFibroblastsStress FibersAdaptor Proteins, Signal Transducingsrc Homology DomainsExtracellular MatrixActininEnzyme InhibitorsBlotting, WesternProtein Structure, TertiaryBacterial AdhesionPrecipitin TestsRecombinant Fusion ProteinsProtein-Serine-Threonine KinasesVanadatesIntracellular Signaling Peptides and ProteinsSerinerhoA GTP-Binding ProteinCell Line, Tumorrho GTP-Binding ProteinsLIM Domain ProteinsProteinsProto-Oncogene ProteinsPhosphatidylinositol 3-KinasesMicrofilament ProteinsProto-Oncogene Proteins c-crkMutationMicroscopy, FluorescenceEndothelium, VascularPseudopodiaImmunoblottingTumor Cells, CulturedProto-Oncogene Proteins c-fynProtein Kinase CRecombinant ProteinsMitogen-Activated Protein KinasesBinding SitesModels, BiologicalGenisteinProtein Tyrosine Phosphatase, Non-Receptor Type 11CadherinsCytochalasin DKineticsGTPase-Activating ProteinsCell MembraneMembrane ProteinsImmunoprecipitationRNA, Small InterferingTime FactorsProtein KinasesMitogen-Activated Protein Kinase 1CricetinaeProto-Oncogene Proteins c-aktCell ShapeActin Cytoskeletonrac1 GTP-Binding ProteinFluorescent Antibody TechniqueEndothelial Cellsrho-Associated KinasesCOS CellsIntegrin beta3Calcium-Calmodulin-Dependent Protein Kinases
KinaseNascent adhesionsProteinsVinculinRegulatesFibersDisassemblyTurnoverComplexesMaturationMediatesRhoAMyosinElongateKinasesIntegrinsSignaling moleculesElongationCytoskeletonSubstrateCorrelatesMolecularOccursRecruitmentMigrationLipidCellPodosomesExpressionRegulationCdc42CellsPathwayActivitySitesStressFoundHighly
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)
  • These studies demonstrate that Rho kinase mediates acid-induced stress fiber formation, which is required for NHE3 exocytosis, and increases in NHE3 activity. (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)
  • 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)
Nascent adhesions7
  • 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)
  • 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)
  • 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)
Proteins4
Vinculin8
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)
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)
  • 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)
  • 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)
  • 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)
Disassembly2
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)
Complexes4
  • 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)
  • 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)
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)
Mediates1
  • Cell-matrix adhesion is the best-studied form of adhesion that mediates cell migration, and is the focus of this outline. (cellmigration.org)
RhoA4
  • 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)
  • 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)
  • 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)
Myosin2
  • 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)
Elongate1
  • 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)
Kinases2
  • 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)
Integrins1
Signaling molecules1
Elongation1
  • Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration. (xenbase.org)
Cytoskeleton2
  • 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)
  • Migration and invasion require coordinated reorganisation of the actin cytoskeleton and regulation of cell-adhesion dynamics. (silverchair.com)
Substrate2
  • 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)
  • Focal adhesions act as molecular clutches that provide grip to the substrate for the lamellipodium to protrude forward during motility. (mechanobio.info)
Correlates1
Molecular2
  • 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)
  • 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)
Occurs1
Recruitment1
  • 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)
Migration5
  • Paxillin is involved in focal adhesion formation during cell adhesion and migration. (ecmbio.com)
  • 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)
  • 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 migration is a fundamental cellular function that is involved in many important biological processes, including embryological development, tissue formation, wound healing, and cancer metastasis. (life-science-alliance.org)
  • 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)
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)
Cell5
  • Both of these sites may be involved in Crk binding to paxillin during integrin-mediated cell adhesion. (ecmbio.com)
  • Owing to their highly localized nature, cell-matrix adhesions were initially called focal adhesions. (cellmigration.org)
  • Over the years, several types of cell-matrix adhesion have been described. (cellmigration.org)
  • In addition it depends on Rac1-mediated cell polarization and lamellipodia formation. (biomedcentral.com)
  • Panel 4 shows sliding of adhesion and hence slight retraction of the respective section of the cell edge compared to panel 3. (mechanobio.info)
Podosomes2
  • The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function. (nature.com)
  • Podosomes are ring-shaped adhesions often found in fast-moving cells, such as macrophages. (cellmigration.org)
Expression2
  • 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)
  • Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation. (uci.edu)
Regulation1
Cdc421
  • The Cdc42 and Rac1 GTPases are required for capillary lumen formation in three-dimensional extracellular matrices. (xenbase.org)
Cells2
  • Cardiovascular function depends on patent blood vessel formation by endothelial cells (ECs). (xenbase.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)
Pathway1
  • We establish a pH dependant oligomerisation pathway forming tetrameric DEC-205 using solution-based techniques and ultimately solved the 4.9 Å cryo-EM structure of the DEC-205 tetramer to identify the unfurling of the second lectin ring which enables tetramer formation. (uci.edu)
Activity1
  • The present studies demonstrate that acid-induced stress fiber formation is required for stimulation of NHE3 activity. (elsevierpure.com)
Sites1
Stress1
Found1
  • 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)
Highly1