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 characteri stic of growth factor stimulation. In this report, we demonstrate that angiotensin II converges with platelet-derived growth factor (PDGF) b eta-receptor signaling cascades, independent of PDGF. Stimulation of s mooth muscle cells with angiotensin II resulted in tyrosine phosphoryl ation 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 p hosphorylation in response to ansotensin II. Immunoblot analyses and p roteolytic digests failed to distinguish this 180-kDa protein from aut hentic PDGF beta-receptors. Corresponding with Shc and PDGF receptor p hosphorylation induced by angiotensin II was the recruitment and phosp horylation of c-Src. Autocrine release of platelet-derived growth fact or failed to account for Shc complex formation at the PDGF receptor fo llowing angiotensin II treatment, and a specific ansotensin II type I receptor antagonist, losartan, abolished the response. These results s upport a novel model for cross-talk between the G-protein-linked ansot ensin II receptor and the PDGF receptor tyrosine kinase in vascular sm ooth muscle cells, Communication with the PDGF receptor may account fo r the ability of angiotensin II to elicit responses typical of growth factor signal transduction.