NERVE GROWTH-FACTOR STIMULATES THE TYROSINE PHOSPHORYLATION OF ENDOGENOUS CRK-II AND AUGMENTS ITS ASSOCIATION WITH P130(CAS) IN PC-12 CELLS

The cellular homologs of the v-Crk oncogene product consist primarily of Src homology region 2 (SH2)(1) and 3 (SH3) domains, v-Crk overexpre ssion causes cell trans formation and elevation of tyrosine phosphoryl ation in fibroblasts and accelerates differentiation of PC-12 cells in response to nerve growth factor (NGF), To further explore the role of Crk in NGF-induced PC-12 cell differentiation, we found that both NGF and epidermal growth factor stimulate the tyrosine phosphorylation of endogenous Crk II. Moreover, hormone stimulation enhanced the specifi c association of Crk proteins with the tyrosine-phosphorylated p130(Ca s), the major phosphotyrosine-containing protein in cells transformed with v-Crk. This interaction is mediated by the SH2 domain of Crk and can be inhibited with a phosphopeptide containing the Crk-SH2 binding motif. Furthermore, the Crk-SH2 domain binds tyrosine-phosphorylated p axillin, a cytoskeletal protein, following treatment of PC-12 cells wi th NGF or epidermal growth factor. These data suggest that Crk functio ns in a number of signaling processes in PC-12 cells.