Cellular ProcessCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signalling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. These signalling events culminate in reorganization of the actin cytoskeleton; a prerequisite for changes in cell shape and motility, and gene expression. Similar morphological alterations and modulation of gene expression are initiated by the binding of growth factors to their respective receptors, emphasizing the considerable crosstalk between adhesion- and growth factor-mediated signalling.
Source: KEGG http://www.genome.jp/kegg/pathway/hsa/hsa04510.htmlb50c61d8ab72bd6c9ea08bffc3ac43be2d05b3db73a93fedd31RAP1A; RAP1A member of RAS oncogene familyRAP1B; RAP1B member of RAS oncogene familyDOCK1; dedicator of cyto-kinesisSHC1; SHC (Src homology 2 domain containing) transforming protein 1SHC3; neuronal ShSOS1; son of sevenless homolog 1 (Drosophila)ZYX; zyxinCAV1; caveolin 1 caveolae protein 22kDCAV3; caveolin 3FYN; FYN oncogene related to SRC FGR YES [EC:2.7.1.112]GRB2; growth factor receptor-bound protein 2VASP; vasodilator-stimulated phosphoproteinSRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [EC:2.7.1.112]ILK; integrin-linked kinase [EC:2.7.1.-]CAV2; caveolin 2VCL; vinculinARAF1; v-raf murine sarcoma 3611 viral oncogene homolog 1 [EC:2.7.1.-]BRAF; v-raf murine sarcoma viral oncogene homolog B1 [EC:2.7.1.-]RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [EC:2.7.1.-]MAPK4; mitogen-activated protein kinase 4 [EC:2.7.1.-]MAPK7; mitogen-activated protein kinase 7 [EC:2.7.1.-SEPP1; selenoprotein P plasmaMAP2K5; mitogen-activated protein kinase kinase 5 [EC:2.7.1.-]MAP2K6; mitogen-activated protein kinase kinase 6 [EC:2.7.1.-MAPK12; mitogen-activated protein kinase 12 [EC:2.7.1.-]MAPK1; mitogen-activated protein kinase 1 [EC:2.7.1.-]MAPK6; mitogen-activated protein kinase 6 [EC:2.7.1.-]MAP2K2; mitogen-activated protein kinase kinase 2 [EC:2.7.1.-]MAP2K3; mitogen-activated protein kinase kinase 3 [EC:2.7.1.-]MAP2K1; mitogen-activated protein kinase kinase 1 [EC:2.7.1.-]PTK2; PTK2 protein tyrosine kinase 2 [EC:2.7.1.11211573199PubMedFibronectin, integrins, and growth control.J Cell Physiol2001Danen EHYamada KM15034601PubMedThe mechanism of action of the tumour suppressor gene PTEN.Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub2003Hlobilkovأƒآ، AKnillovأƒآ، JBأƒآ،rtek JLukأƒآ،s JKolأƒآ،r Z14519391PubMedInteractions between growth factor receptors and adhesion molecules: breaking the rules.Curr Opin Cell Biol2003Comoglio PMBoccaccio CTrusolino L12235283PubMedGet a ligand, get a life: integrins, signaling and cell survival.J Cell Sci2002Stupack DGCheresh DA14744429PubMedRho and Rac take center stage.Cell2004Burridge KWennerberg Kcell adhesion signaling pathwayPW:0000648Pathway Ontology15053919PubMedRegulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase.Biochim Biophys Acta2004Oloumi AMcPhee TDedhar S15459662PubMedIntegrin signalling during tumour progression.Nat Rev Mol Cell Biol2004Guo WGiancotti FG11146675PubMedPaxillin and focal adhesion signalling.Nat Cell Biol2000Turner CE12640026PubMedFocal adhesion kinase: the first ten years.J Cell Sci2003Parsons JT11082269PubMedRho GTPases: signaling, migration, and invasion.Exp Cell Res2000Schmitz AAGovek EEBأƒآ¶ttner BVan Aelst L15179030PubMedMitogenic signal transduction by integrin- and growth factor receptor-mediated pathways.Mol Cells2004Lee JWJuliano R11882383PubMedThe protein kinase B/Akt signalling pathway in human malignancy.Cell Signal2002Nicholson KMAnderson NG11229600PubMedFocal adhesions: structure and dynamics.Biol Cell2000Petit VThiery JP10698680PubMedThe PI3K-PDK1 connection: more than just a road to PKB.Biochem J2000Vanhaesebroeck BAlessi DR15688067PubMedFocal adhesion kinase: in command and control of cell motility.Nat Rev Mol Cell Biol2005Mitra SKHanson DASchlaepfer DD15108811PubMedMultiple connections link FAK to cell motility and invasion.Curr Opin Genet Dev2004Schlaepfer DDMitra SK14756624PubMedIntegrins: structure and signaling.Biochemistry (Mosc)2003Berman AEKozlova NIMorozevich GE