Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor protein tyrosine kinase that acts as a substrate for Src and is a key element of integrin signaling. FAK plays an important role in cell spreading, differentiation, migration, cell death, and acceleration of the G1 to S phase transition of the cell cycle. Tyrosine 397 is the autophosphorylation site of FAK, and involved in its initial activation. This phosphorylated site binds Src family SH2 domains and the p85 subunit of PI3-Kinase, and activates cell migration and invasion. FAK has a central catalytic domain and a C-terminal tail that localizes it to focal adhesions, which are sites where cells attach to the extracellular matrix via surface integrin receptors. Increased FAK tyrosine phosphorylation occurs upon integrin engagement with fibronectin. Adhesion of murine NIH3T3 fibroblasts to fibronectin promotes association of the Grb2 adapter protein and c-Src PTK with FAK in vivo, and also results in activation of the ERK2 MAP kinase. In v-Src-transformed NIH3T3, the association of v-Src, Grb2, and Sos with FAK is independent of cell adhesion to fibronectin. In vitro the Grb2 SH2 domain binds directly to tyrosine-phosphorylated FAK, and the binding site has been identified as Tyr925 by site directed mutagenesis. Several transcript variants encoding different isoforms have been found for the FAK gene, but the full-length natures of only three of them have been determined.
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Protein Aliases: EC 18.104.22.168; FADK 1; FAK-related non-kinase polypeptide; FAK1; Focal adhesion kinase 1; focal adhesion kinase isoform FAK-Del33; focal adhesion kinase pp125FAK; Focal adhesion kinase-related nonkinase; focal ashension kinase 1; FRNK; p125FAK; p41/p43FRNK; pp125FAK; PPP1R71; Protein phosphatase 1 regulatory subunit 71; protein phosphatase 1, regulatory subunit 71; Protein- tyrosine kinase 2; Protein-tyrosine kinase 2; PTK2; PTK2 protein tyrosine kinase 2
Gene Aliases: FADK; FAK; FAK1; FRNK; Kiaa4203; mKIAA4203; p125FAK; pp125FAK; PPP1R71; PTK2; XELAEV_18032408mg; XPFAK