INTEGRINS REGULATE THE ASSOCIATION AND PHOSPHORYLATION OF PAXILLIN BYC-ABL

The c-Abl proto-oncogene is a non-receptor tyrosine kinase whose activ ity and localization are regulated by integrins. Cell adhesion to fibr onectin triggers the transient recruitment of c-Abl from the nucleus t o focal adhesions and activation of its tyrosine kinase. To investigat e the integrin regulation of c-Abl, proteins that interact with c-Abl following cell adhesion were assayed. Several proteins that were phosp horylated 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 respo nse to cell adhesion. In addition, paxillin was found to serve as subs trate for the adhesion-activated c-Abl kinase. These results suggest t hat c-Abl may mediate effects of integrins on cell functions by phosph orylating paxillin.