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Focal Adhesion Kinase 1PaxillinFocal Adhesion Protein-Tyrosine KinasesFocal AdhesionsFocal Adhesion Kinase 2PhosphorylationProtein-Tyrosine KinasesTyrosineCell AdhesionCytoskeletal ProteinsCell Adhesion MoleculesCrk-Associated Substrate ProteinPhosphoproteinsVinculinCytoskeletonSignal TransductionCell Movementsrc-Family KinasesPhosphotyrosineActinsIntegrinsCells, CulturedEnzyme ActivationTalinCell LineAntigens, CD29FibronectinsProtein BindingRetinoblastoma-Like Protein p130Molecular Sequence DataZyxinAmino Acid SequenceTissue AdhesionsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins pp60(c-src)Protein-Serine-Threonine KinasesTransfectionProtein Tyrosine PhosphatasesActininIntercellular Adhesion Molecule-13T3 CellsFibroblastsMicrofilament ProteinsBlotting, Westernsrc Homology DomainsPrecipitin TestsCell Line, TumorProtein Structure, TertiaryExtracellular MatrixAdaptor Proteins, Signal TransducingEnzyme InhibitorsStress FibersRecombinant Fusion ProteinsProtein KinasesProtein Kinase CMAP Kinase Signaling Systemrho GTP-Binding ProteinsrhoA GTP-Binding ProteinVascular Cell Adhesion Molecule-1Intracellular Signaling Peptides and ProteinsProteinsMutationMicroscopy, FluorescenceProto-Oncogene ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein KinasesImmunoblottingCalcium-Calmodulin-Dependent Protein KinasesCytochalasin DProto-Oncogene Proteins c-crkLIM Domain ProteinsBinding SitesProtein Kinase InhibitorsPseudopodiaSerineTumor Cells, CulturedActin CytoskeletonRecombinant ProteinsModels, BiologicalMembrane ProteinsRNA, Small InterferingEndothelium, VascularFluorescent Antibody TechniqueProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-fynVanadatesCell MembraneExtracellular Signal-Regulated MAP KinasesMitogen-Activated Protein Kinase 3Cell ShapeBacterial AdhesionTime Factorsrho-Associated KinasesKineticsGTPase-Activating Proteinsrac1 GTP-Binding ProteinImmunoprecipitationCortactinCadherinsCell Proliferation
Nascent adhesionsVinculinRegulatesComplexesSteroid receptor coactivatorPopulated by integrinSignaling moleculesDynamicsInteractionsMyosinMaturationTurnoverFRNKAdaptor proteinFibersCytoskeletonLamellipodiumMotifsPhosphataseIntegrinsDownstreamResiduesBindsMolecularMigrationSubstrateInteractionOligomerizationRecruitmentGTPasesOccursLipidTargetsDominant-negativeAminoRhoAInitiallyExpressionPathwayRegulationFormationCellsSequenceActivitySitesIncludeShownDomainGene
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)
  • From left: Panel 1 shows formation of nascent adhesions at the cell periphery. (mechanobio.info)
  • Newly formed nascent adhesions gradually grow and change their protein composition to mature into FAs. (life-science-alliance.org)
Vinculin12
Regulates4
  • 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)
  • 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
  • TGFB1I1 is most localized at focal adhesion complexes of cells, although it may be found active in the cytosol, nucleus and cell membrane as well. (wikipedia.org)
  • 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)
  • 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)
Steroid receptor coactivator1
  • 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)
Populated by integrin1
  • 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)
Signaling molecules2
  • These sites may provide docking motifs for recruitment of other signaling molecules to focal adhesions. (ecmbio.com)
  • Gene and protein expression levels of FAK-Src signaling molecules in EL-treated lung cancer cells were determined using PCR arrays, qRT-PCR, and western blotting. (biomedcentral.com)
Dynamics1
Interactions2
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)
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)
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)
FRNK1
  • In this manuscript, we report the generation of a new FAK dominant negative (FF), composed of the C terminus (FRNK) and the FERM domain of the protein. (biologists.com)
Adaptor protein1
  • AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes. (nature.com)
Fibers4
  • 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)
  • 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)
Cytoskeleton2
  • The cytoskeleton is a highly dynamic network of filamentous proteins that enables the active transport of cellular cargo, transduces force, and when assembled into higher-order structures, forms the basis for motile cellular structures that promote cell movement. (mechanobio.info)
  • Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. (biomedcentral.com)
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)
Motifs2
  • 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)
  • All members contain the sequence motifs characteristic of all GTP-binding proteins, bind to GDP and GTP with high affinity. (biomedcentral.com)
Phosphatase1
  • Mechanistically, we found that Rab40c binds the protein phosphatase 6 (PP6) complex and ubiquitylates one of its subunits, ankyrin repeat domain 28 (ANKRD28), thus leading to its lysosomal degradation. (life-science-alliance.org)
Integrins1
Downstream2
  • 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)
  • 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)
Residues2
  • 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)
  • Typically Rho proteins are 190-250 residues long and consist only of the GTPase domain and short terminal C-terminal extensions. (biomedcentral.com)
Binds1
  • Rab40c is a SOCS box-containing protein which binds Cullin5 to form a ubiquitin E3 ligase complex (Rab40c/CRL5) to regulate protein ubiquitylation. (life-science-alliance.org)
Molecular4
  • 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)
  • All molecular weights (MW) are confirmed by comparison to Bio-Rad Rainbow Markers and to western blot mobilities of known proteins with similar MW. (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)
  • My laboratory is focused on understanding mechanisms of resistance to molecular targeting agents directed against receptor tyrosine kinases. (wisc.edu)
Migration8
  • Paxillin is involved in focal adhesion formation during cell adhesion and migration. (ecmbio.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)
  • 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-matrix adhesion is the best-studied form of adhesion that mediates cell migration, and is the focus of this outline. (cellmigration.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)
  • 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)
Substrate1
  • 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)
Interaction1
Oligomerization2
  • Lipid-specific oligomerization of the Marburg virus matrix protein VP40 is regulated by two distinct interfaces for virion assembly. (uci.edu)
  • MARV assembles and buds from the host cell plasma where MARV matrix protein (mVP40) dimers associate with anionic lipids at the plasma membrane inner leaflet and undergo a dynamic and extensive self-oligomerization into the structural matrix layer. (uci.edu)
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)
GTPases2
  • A structural feature that distinguishes the Rho proteins from other small GTPases is the so-called Rho insert domain located between a β strand and an α helix within the small GTPase domain [ 1 - 3 ]. (biomedcentral.com)
  • In turn, GTP-bound active GTPases can interact with a plethora of different effectors which mediate the different cellular functions of this family of proteins. (biomedcentral.com)
Occurs1
Lipid3
  • Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control. (uci.edu)
  • 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)
  • We detected phosphorylation on S155 and identified S155 as a functionally important site for lipid metabolism. (uci.edu)
Targets1
  • However, the exact functions of Rab40c remain to be determined, and what proteins are the targets of Rab40c-Cullin5-mediated ubiquitylation in mammalian cells are unknown. (life-science-alliance.org)
Dominant-negative1
Amino1
  • Within their GTPase domains, they share approximately 30% amino acid identity with the Ras proteins and 40-95% identity within the family. (biomedcentral.com)
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)
Initially1
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)
Pathway1
  • 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)
Regulation1
Formation2
Cells5
  • Podosomes are ring-shaped adhesions often found in fast-moving cells, such as macrophages. (cellmigration.org)
  • 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)
  • Glucocorticoid-induced TNFR family-related protein (GITR)-mediated activation of c-Jun N-terminal kinase (JNK) was shown to regulate the suppressive activity of naturally occurring CD4+CD25+ T regulatory cells (nTregs) in wild-type (WT) hosts. (siamtech.net)
  • We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. (uci.edu)
  • DEC-205 (CD205), a member of the macrophage mannose receptor protein family, is the prototypic endocytic receptor of dendritic cells, whose ligands include phosphorothioated cytosine-guanosine (CpG) oligonucleotides, a motif often seen in bacterial or viral DNA. (uci.edu)
Sequence1
Activity2
  • Cytokines such as for example IL-6 (21-23) and surface area proteins such as for example Compact disc8 (5 24 are also shown to influence nTreg activity. (siamtech.net)
  • Activation of c-Jun N-terminal kinase (JNK) following GITRL ligation of GITR was associated with the Mouse monoclonal to LPA loss of suppressive activity (9). (siamtech.net)
Sites2
Include1
  • Rho GTPase effectors are a large group of proteins and include actin nucleation promoting molecules, adaptors, as well as kinases. (biomedcentral.com)
Shown1
  • 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)
Domain1
  • 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)
Gene1
  • Transforming growth factor beta-1-induced transcript 1 protein is a protein that in humans is encoded by the TGFB1I1 gene. (wikipedia.org)