Convergence of Angiotensin II and Platelet-derived Growth Factor Receptor Signaling Cascades in Vascular Smooth Muscle Cells

Abstract

Signaling cascades elicited by angiotensin 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 Shc proteins and subsequent complex formation between Shc and growth factor receptor binding protein-2 (GRB2). A 180-kDa protein co-precipitating with Shc.GRB2 complexes also demonstrated increased phosphorylation in response to angiotensin 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 angiotensin II type I receptor antagonist, losartan, abolished the response. These results support a novel model for cross-talk between the G-protein-linked angiotensin 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.