INTEGRIN-MEDIATED SIGNAL-TRANSDUCTION IN CELLS LACKING FOCAL ADHESIONKINASE P125(FAK)

We have previously shown that integrin-dependent tyrosine phosphorylat ion of p130(Cas) (Cas) could be induced in a mouse fibroblast cell lin e that does not express focal adhesion kinase p125(FAK) (FAK). By anal yzing FAK-deficient (FAK-/-) cells transiently expressing Cas mutant p roteins, we demonstrate here that the Src homology 3 (SH3) domain of C as is indispensable for adhesion-mediated Cas phosphorylation in this mutant cell line. While the FAK directly binds to Cas-SH3, our finding s imply that SH3-binding molecule(s) other than FAK might regulate Cas phosphorylation, at least in FAK-/- cells. In this regard, we observe d that FAK-/- cells expressed cell adhesion kinase beta (CAK beta), a protein tyrosine kinase of the FAK subfamily. CAK beta expressed by FA K-/- cells was associated in vivo with Cas in a Cas-SH3-dependent mann er, Moreover, integrin stimulation induces tyrosine phosphorylation of CAK beta in FAK-/- cells. Thus, our results suggest that CAK beta con tributes to integrin-mediated signal transduction in place of FAK in F AK-deficient cells, (C) 1998 Federation of European Biochemical Societ ies.