SRC KINASE PLAYS AN ESSENTIAL ROLE IN INTEGRIN-MEDIATED TYROSINE PHOSPHORYLATION OF CRK-ASSOCIATED SUBSTRATE P130(CAS)

A novel signaling molecule p130(Cas) has been shown to undergo tyrosin e phosphorylation in response to integrin-mediated cell adhesion. In t his study, we have attempted to identify kinases that mediate Cas phos phorylation in integrin signaling by examining various mutant cell lin es that do not express either p125(FAK) c-Src, c-Fyn or c-Abl. We foun d that deficiency of c-Src but not of other kinases completely abrogat ed integrin-mediated Cas phosphorylation. Importantly, paxillin phosph orylation was not compromised in each mutant cell line examined. These results suggest that c-Src primarily mediates adhesion-dependent Cas phosphorylation. As for paxillin phosphorylation, there may exist subs tantial redundancy amongst multiple kinases. Finally, adhesion-induced Cas phosphorylation resulted in its association with the c-Crk adapte r protein via the Crk-SH2 domain. Thus, Cas plays a role in the transm ission of integrin-initiated signals through tyrosine phosphorylation and subsequent binding to c-Crk. (C) 1996 Academic Press. Inc.