Reactivation of host-dependent src kinase activity by co-expression with a heterologous tyrosine kinase

Abstract

XD4 is a host range deletion mutant (delta 77-225) of the v-src transforming gene. This mutant transforms chicken embryo fibroblasts (CEF) but not Rat-2 cells. It encodes a product (XD4-src) that is phosphorylated at tyrosine and active as a tyrosine kinase in CEF, but is neither phosphorylated at tyrosine nor active as a kinase in Rat-2 cells. We report here that the XD4-src kinase activity in Rat-2 cells can be restored by co-expression with the tyrosine kinase encoded by v-fps, but not by co-expression with activated Ha-ras. Mutation of the major tyrosine autophosphorylation site (Y416) in XD4-src reduced but did not abolish the reactivation of XD4 tyrosine phosphorylation and kinase activity by v-fps. These results suggest that deletion of the SH2 and SH3 domains renders v-src kinase activity dependent on tyrosine phosphorylation at Y416 and other sites. The reactivation of XD4-src may result either from direct phosphorylation by the v-fps gene product or may be an indirect consequence of v-fps expression.