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 FAK Signaling

Focal adhesion kinase-1 (FAK) is activated by focal adhesion complex (FAC)-associated growth factors and integrins. FAK is constitutively associated with b-integrin subunits of integrin receptors. The binding to integrins of components of the extracellular matrix (ECM) leads to activation of FAK. The activation of FAK may be further enhanced by the co-stimulation of growth factor receptors by ECM associated growth factors, such as bFGF, EGF or PDGF.

FAK is a non-receptor protein tyrosine kinase (NRPTK) that is typically, but not always, associated with supramolecular focal adhesion (FA) complexes (FAC). Focal adhesion complex assembly and disassembly are critical for cell attachment and movement. FAK does not phosphorylate other proteins. However, when FAK is activated it autophosphorylates and binds Src kinase which in turn phosphorylates other sites on FAK and the FAK-binding proteins, Cas and paxillin. Phosphorylated FAK becomes a docking site within focal adhesion complexes for mediators of multiple signaling events that regulate growth, survival and morphogenesis.

FAK is involved in the regulation of cell growth and survival through activation of PI3K/PKD1/Akt/PKB and Grb2/SOS/Ras/Raf-1/MEK/ERK pathways. FAK mediates cells motility and adhesion turnover through regulation of the RhoGTPases, especially RhoA, Rac-1 and Cdc42. FAK affects the down-regulation of stress fiber formation mediated by RhoA by activating RhoAGAP, GRAF (GTPase regulator associated with focal adhesion kinase). FAK upregulates the formation of lamellipodia by activating Rac-1 via a Cas-Crk-DOCK-ELMO complex. Rac-1 also promotes cell survival and growth at the level of MEK/ERK activation.