Focal adhesion kinase (FAK) is a widely expressed cytoplasmic protein tyrosine kinase involved in signal transduction pathways important for cell spreading, migration and survival. Activation of FAK by integrin clustering leads to autophosphorylation at Tyr-397, which is a binding site for Src family kinases, PI3-Kinase, and PLCγ. The recruitment of Src family kinases results in the phosphorylation of tyrosine 407, 576, and 577 in the catalytic domain, and tyrosine 871 and 925 in the carboxy-terminal region of FAK. Thus, the phosphorylation of Tyr-397 is a critical step in the activation of FAK.