Tyrosine phosphorylation and association of p130Cas and c-Crk II by ANG II in vascular smooth muscle cells

In cultured vascular smooth muscle cells (VSMC), angiotensin II (ANG II) stimulated tyrosine phosphorylation of multiple proteins including a 130-kDa protein. This 130-kDa protein was identified as a Crk-associated substrate, p130(Cas). ANG II-stimulated tyrosine phosphorylation of p130(Cas) was rapid, concentration dependent, and inhibited by the AT(1)-receptor antagonist CV-11974. Neither downregulation of protein kinase C by long exposure of cells to phorbol 12,13-dibutyrate nor blockade of Ca2+ mobilization by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester had an effect on ANG II-stimulated tyrosine phosphorylation of p130(Cas). Stimulation with ANG II enhanced the specific association of p130(Cas) with c-Crk II. The time course of the association of p130(Cas) and c-Crk II was similar to that of tyrosine phosphorylation of p130(Cas). c-Crk II was also tyrosine phosphorylated in response to ANG II. These results indicate that ANG II induces tyrosine phosphorylation of p130(Cas) and c-Crk II and their specific association, suggesting a potential role of the p130(Cas)-c-Crk II complex in ANG II signal transduction in VSMC.