STIMULATION OF CELL-MIGRATION BY OVEREXPRESSION OF FOCAL ADHESION KINASE AND ITS ASSOCIATION WITH SRC AND FYN

Cellular interactions with the extracellular matrix proteins play impo rtant roles in a variety of biological processes. Recent studies sugge st that integrin-mediated cell-matrix interaction can transduce bioche mical signals across the plasma membrane to regulate cellular function s such as proliferation, differentiation and migration. These studies have implicated a critical role of focal adhesion kinase (FAK) in inte grin-mediated signal transduction pathways. We report here that overex pression of FAK in CHO cells increased their migration on fibronectin. A mutation of the major autophosphorylation site Y397 in FAK abolishe d its ability to stimulate cell migration, while phosphorylation of Y3 97 in a kinase-defective FAK by endogenous FAK led to increased migrat ion. We also find that the wild-type and the kinase-defective FAK were associated with Src and Fyn in CHO cells whereas the F397 mutant was not. These results directly demonstrate a functional role for FAK in i ntegrin signaling leading to cell migration. They also provide evidenc e for the functional significance of FAK/Src complex formation in vivo .