Integrin-mediated signal transduction in cells lacking focal adhesion kinase p125 FAK

Abstract

We have previously shown that integrin-dependent tyrosine phosphorylation of p130 Cas (Cas) could be induced in a mouse fibroblast cell line that does not express focal adhesion kinase p125 FAK (FAK). By analyzing FAK-deficient (FAK−/−) cells transiently expressing Cas mutant proteins, we demonstrate here that the Src homology 3 (SH3) domain of Cas is indispensable for adhesion-mediated Cas phosphorylation in this mutant cell line. While the FAK directly binds to Cas-SH3, our findings imply that SH3-binding molecule(s) other than FAK might regulate Cas phosphorylation, at least in FAK−/− cells. In this regard, we observed that FAK−/− cells expressed cell adhesion kinase β (CAKβ), a protein tyrosine kinase of the FAK subfamily. CAKβ expressed by FAK−/− cells was associated in vivo with Cas in a Cas-SH3-dependent manner. Moreover, integrin stimulation induces tyrosine phosphorylation of CAKβ in FAK−/− cells. Thus, our results suggest that CAKβ contributes to integrin-mediated signal transduction in place of FAK in FAK-deficient cells.