FOCAL ADHESION KINASE AND PAXILLIN BIND TO PEPTIDES MIMICKING BETA-INTEGRIN CYTOPLASMIC DOMAINS

The integrins have recently been implicated in signal transduction. A likely mediator of integrin signaling is focal adhesion kinase (pp125( FAK) Or FAK), a structurally distinct protein tyrosine kinase that bec omes enzymatically activated upon engagement of integrins with their l igands, A second candidate signaling molecule is paxillin, a focal adh esion associated, cytoskeletal protein that coordinately becomes phosp horylated on tyrosine upon activation of pp125(FAK). Paxillin physical ly complexes with two protein tyrosine kinases, pp60(src) and Csk (COO H-terminal src kinase), and the oncoprotein p47(gag-crk), each of whic h could function as part of a paxillin signaling complex. Using an in vitro assay we have established that the cytoplasmic domain of the bet a(1) integrin can bind to paxillin and pp125(FAK) from chicken embryo cell lysates, The NH2-terminal, noncatalytic domain of pp125(FAK) can bind directly to the cytoplasmic tail of beta(1) and recognizes integr in sequences distinct from those involved in binding to alpha-actinin. Paxillin binding is independent of pp125(FAK) binding despite the fac t that both bind to the same region of beta(1). These results demonstr ate that the cytoplasmic domain of the beta subunits of integrins cont ain binding sites for both signaling molecules and structural proteins suggesting that integrins can coordinate the generation of cytoplasmi c signals in addition to their role in anchoring components of the cyt oskeleton.