Angiotensin II controls p21(ras) activity via pp60(c-src)

Angiotensin II is the major effector peptide of the renin-angiotensin system, and it exerts its physiologic functions via a G protein-coupled cell surface receptor called AT(1). We found that in rat aortic smooth muscle cells, angiotensin II stimulated the formation of Ras-GTP, Ras-Raf-1 complex formation, and the tyrosine phosphorylation of two important has GTPase activating proteins (GAPs), p120 Ras-GAP and p190 Rho-GAP. Electroporation of anti-pp60(c-src) antibody into cultured, adherent smooth muscle cells blocked the angiotensin II stimulation of Ras-GAP and Rho-GAP tyrosine phosphorylation. In contrast electroporation of antibodies against c-Yes or c-Fyn had no effect. Anti-pp60(c-src) antibody also blocked angiotensin II-stimulated Ras activation and Ras Raf-1 complex formation. These data strongly suggest that a G protein-coupled receptor such as the AT(1) receptor can activate the Ras protein cascade via the tyrosine kinase pp60(c-src).