THE RELATED ADHESION FOCAL TYROSINE KINASE IS TYROSINE-PHOSPHORYLATEDAFTER BETA-1-INTEGRIN STIMULATION IN B-CELLS AND BINDS TO P130(CAS)

Integrin ligation initiates intracellular signaling events, among whic h are the activation of protein tyrosine kinases. The related adhesion focal tyrosine kinase (RAFTK), also known as PYK2 and CAK beta, is a tyrosine kinase that is homologous to the focal adhesion kinase (FAK) p125(FAK). The structure of RAFTK is similar to p125(FAK) in that it l acks a transmembrane region, does not contain Src homology 2 or 3 doma ins, and has a proline rich region in its C terminus. Here we report t hat RAFTK is a target for beta 1-integrin-mediated tyrosine phosphoryl ation in both transformed and normal human B cells. Ligation of the B cell antigen receptor also induced tyrosine phosphorylation of RAFTK. Phosphorylation of RAFTK following integrin- or B cell antigen recepto r-mediated stimulation was decreased by prior treatment of cells with cytochalasin B, indicating that this process was at least partially cy toskeleton-dependent. One of the tyrosine-phosphorylated substrates af ter integrin stimulation in fibroblasts is p130(cas), which can associ ate with p125(FAK). RAFTK also interacted constitutively with p130(cas ) in B cells, since p130(cas) was detected in RAFTK immunoprecipitates . Although the function of RAFTK remains unknown, these data suggest t hat RAFTK may have a significant function in integrin-mediated signali ng pathways in B cells.