Integrins regulate the association and phosphorylation of paxillin by c-Abl.

The c-Abl proto-oncogene is a non-receptor tyrosine kinase whose activity and localization are regulated by integrins. Cell adhesion to fibronectin triggers the transient recruitment of c-Abl from the nucleus to focal adhesions and activation of its tyrosine kinase. To investigate the integrin regulation of c-Abl, proteins that interact with c-Abl following cell adhesion were assayed. Several proteins that were phosphorylated on tyrosine were found to transiently co-precipitate with c-Abl during cell adhesion, and one was identified as the focal adhesion protein paxillin. Abl also became transiently phosphorylated in response to cell adhesion. In addition, paxillin was found to serve as substrate for the adhesion-activated c-Abl kinase. These results suggest that c-Abl may mediate effects of integrins on cell functions by phosphorylating paxillin.