Focal adhesion kinase in integrin signaling.

Focal adhesion kinase (FAK) has recently been established as a key component of the signal transduction pathways triggered by integrins. Aggregation of integrins and the cytoskeletal proteins tensin, paxillin and talin is proposed to be responsible for FAK activation and autophosphorylation by integrins in cell adhesion. Activation and autophosphorylation of FAK lead to its binding to a number of intracellular signaling molecules, including Src, Grb2 and PI 3-kinase. FAK/Src association activates both kinases, which act on the potential substrates tensin, paxillin and p130cas. Besides cytoskeletal regulation, FAK phosphorylation of paxillin and p130cas could also lead to MAP kinase pathway by adaptor proteins such as Crk and Nck. Recent studies indicated that integrin signaling through FAK causes increased cell migration and potentially regulates cell proliferation and survival. Future challenges will include clarifying the roles of signaling pathways downstream of FAK in cell migration and cell cycle regulation.