INTERACTION OF FOCAL ADHESION KINASE WITH CYTOSKELETAL PROTEIN TALIN

The interaction of cells with extracellular matrix proteins plays a cr itical role in a variety of biological processes. Recent studies sugge st that cell-matrix interactions mediated by integrins can transduce b iochemical signals to the cell interior that regulate cell proliferati on and differentiation. These studies have placed the focal adhesion k inase (FAR), an intracellular protein tyrosine kinase, in a central po sition in integrin-initiated signal transduction pathways (Zachary, I. , and Rozengurt, E. (1992) Cell 71, 891-894; Schaller, M., and Parsons , J. T. (1993) Trends Cell Biol. 3, 258-262). Here, we report data sug gesting a possible association of FAK with the cytoskeletal protein ta lin in NIH 3T3 cells. We have identified a 48-amino acid sequence in t he carboxyl-terminal domain of FAK necessary for talin binding in vitr o. Furthermore, we have correlated the ability of integrin to induce F AR phosphorylation with its ability to bind talin using a mutant integ rin lacking the carboxyl-terminal 13 amino acids. These studies sugges t talin may be a mediator for FAK activation in signaling initiated by integrins and may provide an explanation for the dependence on the in tegrity of actin-cytoskeleton of multiple intracellular signaling path ways converging to FAK activation and autophosphorylation.