CONVERGENCE OF ANGIOTENSIN-II AND PLATELET-DERIVED GROWTH-FACTOR RECEPTOR SIGNALING CASCADES IN VASCULAR SMOOTH-MUSCLE CELLS

Signaling cascades elicited by ansotensin II resemble those characteristic of growth factor stimulation. In this report, we demonstrate that angiotensin II converges with platelet-derived growth factor (PDGF) beta-receptor signaling cascades, independent of PDGF. Stimulation of smooth muscle cells with angiotensin II resulted in tyrosine phosphorylation on She proteins and subsequent complex formation between She and growth factor receptor binding protein a (GRB2). A 180-kDa protein co-precipitating with Shc . GRB2 complexes also demonstrated increased phosphorylation in response to ansotensin II. Immunoblot analyses and proteolytic digests failed to distinguish this 180-kDa protein from authentic PDGF beta-receptors. Corresponding with Shc and PDGF receptor phosphorylation induced by angiotensin II was the recruitment and phosphorylation of c-Src. Autocrine release of platelet-derived growth factor failed to account for Shc complex formation at the PDGF receptor following angiotensin II treatment, and a specific ansotensin II type I receptor antagonist, losartan, abolished the response. These results support a novel model for cross-talk between the G-protein-linked ansotensin II receptor and the PDGF receptor tyrosine kinase in vascular smooth muscle cells, Communication with the PDGF receptor may account for the ability of angiotensin II to elicit responses typical of growth factor signal transduction.