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Focal Adhesion Protein-Tyrosine KinasesFocal AdhesionsFocal Adhesion Kinase 1TyrosineProtein-Tyrosine KinasesCell AdhesionPhosphorylationPaxillinCell Adhesion MoleculesFocal Adhesion Kinase 2Signal Transductionsrc-Family KinasesPhosphatidylinositol 3-KinasesReceptor Protein-Tyrosine KinasesProtein Kinase InhibitorsVinculinPhosphotyrosineCell MovementProtein-Serine-Threonine KinasesMAP Kinase Signaling SystemPhosphoproteinsEnzyme ActivationCells, CulturedProtein Tyrosine PhosphatasesProtein KinasesCell LineCytoskeletal ProteinsIntegrinsMolecular Sequence DataCalcium-Calmodulin-Dependent Protein KinasesCrk-Associated Substrate ProteinTissue AdhesionsProto-Oncogene ProteinsProtein BindingProto-Oncogene Proteins pp60(c-src)Amino Acid SequenceTransfectionIntercellular Adhesion Molecule-1Enzyme InhibitorsActinsMitogen-Activated Protein Kinase 1Protein Kinase Csrc Homology DomainsGenisteinMutation3T3 CellsReceptor, Epidermal Growth FactorCell Line, TumorCytoskeletonZyxinFibronectinsProtein Structure, TertiaryIntracellular Signaling Peptides and ProteinsPyrimidinesRecombinant Fusion ProteinsBlotting, WesternProto-Oncogene Proteins c-ablMitogen-Activated Protein Kinase 3Adaptor Proteins, Signal TransducingAntigens, CD29Lymphocyte Specific Protein Tyrosine Kinase p56(lck)p38 Mitogen-Activated Protein KinasesMitogen-Activated Protein KinasesProto-Oncogene Proteins c-fynFibroblastsTyrosine 3-MonooxygenaseVascular Cell Adhesion Molecule-1TalinTumor Cells, Culturedp21-Activated KinasesPrecipitin TestsCyclic AMP-Dependent Protein KinasesRecombinant ProteinsJNK Mitogen-Activated Protein KinasesMitogen-Activated Protein Kinase KinasesBinding SitesBase SequenceKineticsExtracellular Signal-Regulated MAP Kinasesrho-Associated KinasesStress FibersRetinoblastoma-Like Protein p130ImmunoblottingCell DivisionProteinsExtracellular MatrixTyrphostinsModels, Biologicalfms-Like Tyrosine Kinase 3Proto-Oncogene Proteins c-aktApoptosisrhoA GTP-Binding ProteinBenzamidesBacterial AdhesionRNA, MessengerMembrane ProteinsVanadatesEndothelium, VascularPiperazinesTime Factors

Protein tyrosine phProline-richPhosphorylationReceptor tyrosinRegulatesPyk2Cytoplasmic proteinMAPKSignal TransductionPhosphatidylinositolCytoskeletonPaxillinActinSerineProteinsResiduesReceptorsExtracellular matrixIntegrinsLocalizationInvolved in cell adhesionSubfamilyMoleculeAbstractProto-oncogeneCollagenActivationSubstratePathwaysComplexesInvasionClosely-relatedEnzymeFilopodiaSurvivalGrowthCell cycleActivityDifferentiationFibersNuclearCells

Protein tyrosine ph1

• Most tyrosine kinases have an associated protein tyrosine phosphatase, which removes the phosphate group. (wikipedia.org)

Proline-rich1

• N. Boutahar, A. Guignandon, L. Vico, M. H. Lafage-ProustMechanical strain on osteoblasts activates autophosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 tyrosine sites involved in ERK activationIn J Biol Chem, volume 279, 2004. (fau.de)

Phosphorylation13

• Phosphorylation of proteins by kinases is an important mechanism for communicating signals within a cell (signal transduction) and regulating cellular activity, such as cell division. (wikipedia.org)
• Tyrosine kinases catalyze the phosphorylation of tyrosine residues in proteins. (wikipedia.org)
• The phosphorylation of tyrosine residues in turn causes a change in the function of the protein that they are contained in. (wikipedia.org)
• Phosphorylation at tyrosine residues controls a wide range of properties in proteins such as enzyme activity, subcellular localization, and interaction between molecules. (wikipedia.org)
• It has also been demonstrated that phosphorylation of a middle-T antigen on tyrosine is also associated with cell transformation, a change that is similar to cellular growth or reproduction. (wikipedia.org)
• The binding of extracellular matrix ligands to integrins triggers autophosphorylation at Tyr-397, and activation of FAK through phosphorylation of Tyr residues (Tyr-576 and Tyr577) in the kinase domain activation loop. (fishersci.com)
• For example, cell adhesion to a fibronectin substratum involves concurrent activation of Src and phosphorylation of the FAK activation loop. (fishersci.com)
• In addition, phosphorylation of other Tyr residues (Tyr-925, and Tyr-861) creates binding sites for SH2 domains of intracellular signaling molecules such as Src, PI3 kinase, and Grb2. (fishersci.com)
• Thus, FAK activity is regulated by a complex set of phosphorylation sites, and thisphospho-regulation could be important for cell motility, cell growth, cytoskeletal organization, and adhesion-dependent cell survival. (fishersci.com)
• Both vinY822F and vin −/− cells exhibit increased interaction between paxillin and focal adhesion kinase (FAK) and increased paxillin and FAK phosphorylation. (rupress.org)
• Tyrosine kinases Fyn and FAK interact with NCAM and undergo phosphorylation and this transiently activates the MAPK, ERK 1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. (uni-freiburg.de)
• The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. (uni-freiburg.de)
• We demonstrate that DARPP-32 inhibits MCF-7 cell migration and that this effect requires phosphorylation of Threonine-34, an event catalyzed by protein kinase A (PKA) and strongly induced by detachment of cells from the culture substrate. (lu.se)

Receptor tyrosin4

• 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)
• The receptor tyrosine kinases function in transmembrane signaling, whereas tyrosine kinases within the cell function in signal transduction to the nucleus. (wikipedia.org)
• Non-receptor tyrosine kinases and the actin cytoskeleton in contractile vascular smooth muscle. (manchester.ac.uk)
• Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. (gla.ac.uk)

Regulates2

• Integrin-mediated adhesion to extracellular matrix regulates the migration and proliferation of many cell types, but its role in glioma progression is undefined. (elsevierpure.com)
• Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that regulates cell signaling, proliferation, migration, and development. (rcsb.org)

Pyk24

• We investigated the role of the cytoplasmic tyrosine kinases FAK and Pyk2, potential integrin effectors, in the phenotypic determination of four different human glioblastoma cell lines. (elsevierpure.com)
• 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)
• In the present study, we used a knockout murine model to analyze the contribution of the Ca2+-dependent focal adhesion kinase Pyk2 in platelet activation and thrombus formation in vivo. (edu.au)

Cytoplasmic protein2

• Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling through integrins. (embl.de)
• This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. (genetex.com)

MAPK2

• These events are influenced by and activate other molecular pathways, including phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK),[2] and therapies are now available that target these pathocellular processes. (cancernetwork.com)
• In recent work, we have examined aspects of the regulation of mitogen-activated protein kinases (MAPK), mammalian target of rapamycin (mTOR), and integrin-dependent signaling by muscarinic receptor subtypes. (bu.edu)

Signal Transduction2

• Furthermore, tyrosine kinases function in many signal transduction cascades wherein extracellular signals are transmitted through the cell membrane to the cytoplasm and often to the nucleus, where gene expression may be modified. (wikipedia.org)
• Lyn and Src family tyrosine kinases in general have been known to function in signal transduction pathways. (wikipedia.org)

Phosphatidylinositol4

• Upon autophagy activation, Atgs, serine/threonine kinase ULK1, and Beclin-1, in association with Atg14 and type III phosphatidylinositol 3-kinase Vps34, promote the formation of a cup-shaped isolation membrane to engulf the cargo ( 1 ). (frontiersin.org)
• Phosphatidylinositol 3-kinaseβ (PI3Kβ) plays a predominant role in integrin outside-in signaling and in platelet activation by GPVI engagement. (edu.au)
• DLL-4, in turn, instigated neighbouring platelets to switch to 'activated' phenotype through cleavage of Notch receptor and release of its intracellular domain (NICD), which was averted by inhibition of γ-secretase and phosphatidylinositol-3-kinase (PI3K). (elifesciences.org)
• PI-3K, phosphatidylinositol-3 kinase. (rupress.org)

Cytoskeleton2

• Protein-tyrosine phosphatases PTPN3 and PTPN4, enzyme that appear to act at junctions between the membrane and the cytoskeleton. (embl.de)
• Although previous studies have identified different chemotropic and adhesion molecules that influence axonal development, the molecular mechanism by which these signals control the cytoskeleton remains poorly understood. (biologists.com)

Paxillin1

• 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)

Actin1

• 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)

Serine2

• Tyrosine kinases belong to a larger class of enzymes known as protein kinases which also attach phosphates to other amino acids such as serine and threonine. (wikipedia.org)
• The enzymes fall into two broad classes, characterised with respect to substrate specificity: serine/threonine-specific, and tyrosine-specific (the subject of this article). (wikipedia.org)

Proteins5

• A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. (wikipedia.org)
• proteins in the cytosol and proteins in the nucleus are phosphorylated at tyrosine residues during this process. (wikipedia.org)
• FAK's ability to bind numerous structural and signaling proteins via a variety of interactions is important for FAK activation level, and for FAK interaction with a variety of substrates localized to sites of cell adhesion. (fishersci.com)
• Other components include signalling molecules such as tyrosine-kinases, GTPases and effectors proteins as in focal adhesion. (u-bordeaux.fr)
• 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)

Residues2

• Protein kinases are a group of enzymes that possess a catalytic subunit that transfers the gamma (terminal) phosphate from nucleoside triphosphates (often ATP) to one or more amino acid residues in a protein substrate side-chain, resulting in a conformational change affecting protein function. (wikipedia.org)
• We identified a network of mainly charged residue-residue interactions spanning from the PIP₂ binding site to the distant interface between the kinase and FERM domains, comprising candidate residues for mutagenesis to validate the predicted mechanism of FAK activation. (rcsb.org)

Receptors2

• Janus tyrosine kinases (JAKs), cytoplasmic tyrosine kinases that are non-covalently associated with the cytoplasmic tails of receptors for cytokines or polypeptidic hormones. (embl.de)
• Work from my laboratory and others has established roles for G protein-coupled (including muscarinic) receptors, growth factor receptors, protein kinases and calcium influx as activators of APP ectodomain shedding. (bu.edu)

Extracellular matrix2

• Fibroblasts - a type of cell that synthesizes the extracellular matrix and collagen and is involved in wound healing - that have been transformed by the polyomavirus possess higher tyrosine activity in the cellular matrix. (wikipedia.org)
• Upon cell adhesion to the extracellular matrix, FAK is being translocated toward focal adhesion sites and activated. (rcsb.org)

Integrins1

• Focal Adhesion Kinase (FAK) is a cytoplasmic tyrosine kinase that colocalizes with integrins in focal adhesions. (fishersci.com)

Localization2

• A protein tyrosine kinase called pp125, also referred to as focal adhesion kinase (FAK) is likely at hand in the influence of cellular focal adhesions, as indicated by an immunofluorescent localization of FAK. (wikipedia.org)
• This cellular localization is directed by a 125 amino acid sequence at the C-terminus called the "Focal Adhesion Targeting" sequence (FAT). (fishersci.com)

Involved in cell adhesion1

• In addition, their osteogenic differentiation potential was increased, and genes involved in cell adhesion, FGF-2 signalling, cell cycle, stemness, cell differentiation, and cell proliferation were upregulated, compared to that of the MSCs cultured on uncoated plates. (hindawi.com)

Subfamily2

• The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. (genetex.com)
• The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. (cancerindex.org)

Molecule2

• Kinase is a large family of enzymes that are responsible for catalyzing the transfer of a phosphoryl group from a nucleoside triphosphate donor, such as ATP, to an acceptor molecule. (wikipedia.org)
• The neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the nervous system. (uni-freiburg.de)

Abstract1

• abstract = "We speculated that focal adhesion kinase (FAK) might play a critical role in the TNFα-induced cell death. (elsevierpure.com)

Proto-oncogene1

• The cellular sarcoma gene (SRC) is a proto-oncogene encoding for a tyrosine kinase. (jcancer.org)

Collagen2

• Slack, B.E., Siniaia, M.S., and Blusztajn, J.K. (2006) Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor I: Involvement of Src tyrosine kinase. (bu.edu)
• Moreover, Wnt-5a is known to inhibit migration of breast epithelial cells in culture and expression of Wnt-5a potentiates activation of the receptor tyrosine kinase DDR1, a collagen receptor implicated in cell adhesion and migration. (lu.se)

Activation1

• Inhibition of cell/substrate adhesion with specific anti-integrin antibodies demonstrated that P-FAKSer732 activation is not induced by integrin clustering. (aacrjournals.org)

Substrate2

• Focal adhesions act as molecular clutches that provide grip to the substrate for the lamellipodium to protrude forward during motility. (mechanobio.info)
• Thaw the Active FAK, Kinase Assay Buffer III (5X), and Substrate on ice. (rndsystems.com)

Pathways1

• Tyrosine kinases function in a variety of processes, pathways, and actions, and are responsible for key events in the body. (wikipedia.org)

Complexes2

• In addition to stress fibers, rho controls the assembly of focal adhesion complexes. (nih.gov)
• We now show that rac and cdc42 also stimulate the assembly of multimolecular focal complexes at the plasma membrane. (nih.gov)

Invasion1

• Podosomes are found in a restricted number of cell types (macrophages, immature dendritic cells and osteoclasts) where they seem to be involved in adhesion and invasion. (u-bordeaux.fr)

Closely-related1

• Src family tyrosine kinases are closely related but demonstrate a wide variety of functionality. (wikipedia.org)

Enzyme1

• Prepare a 15 μL enzyme dilution with Kinase Dilution Buffer X (1X) at the desired concentration, with Kinase Dilution Buffer X (1X), in a pre-chilled 96-well plate. (rndsystems.com)

Filopodia1

• Finally, we found that phospho-DARPP-32 inhibited the activity of the focal adhesion kinase (FAK) in MCF-7 breast cancer cells, and that MCF-7 cells expressing phospho-DARPP-32 displayed less filopodia formation. (lu.se)

Survival1

• Here, we show that vinculin null (vin −/− ) cells and cells expressing a vinculin Y822F mutant have increased survival due to up-regulated activity of extracellular signal-regulated kinase (ERK). (rupress.org)

Growth4

• Protein kinases can become mutated, stuck in the "on" position, and cause unregulated growth of the cell, which is a necessary step for the development of cancer. (wikipedia.org)
• Cellular growth and reproduction may rely to some degree on tyrosine kinase. (wikipedia.org)
• Roles or expressions of Src family tyrosine kinases vary significantly according to cell type, as well as during cell growth and differentiation. (wikipedia.org)
• The establishment of neural circuits depends on the ability of axonal growth cones to sense their surrounding environment en route to their target. (biologists.com)

Cell cycle2

• Tyrosine kinase activity in the nucleus involves cell-cycle control and properties of transcription factors. (wikipedia.org)
• To be specific, Lyn, a type of kinase in the Src family that was identified in the nuclear matrix, appears to control the cell cycle. (wikipedia.org)

Activity2

• Furthermore, tyrosine kinase activity has been determined to be correlated to cellular transformation. (wikipedia.org)
• Determine the corrected activity (RLU) by removing the blank control value (see step 4) for each sample and calculate the kinase specific activity as outlined below. (rndsystems.com)

Differentiation1

• The ECM provides structural and biochemical support to the cells and has various other functions including cell adhesion, cell to cell communication, and differentiation [ 17 , 18 ]. (hindawi.com)

Fibers1

• 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)

Nuclear1

• Tyrosine kinase function has been observed in the nuclear matrix, which comprises not the chromatin but rather the nuclear envelope and a "fibrous web" that serves to physically stabilize DNA. (wikipedia.org)

Cells1

• FAK seems also to have a role in the proliferation of tumor cells by its biochemical and biological association to cytoplasmic kinases such as src and ERK. (aacrjournals.org)