Angiotensin II induces transactivation of two different populations of theplatelet-derived growth factor beta receptor - Key role for the p66 adaptor protein Shc

Several signal transduction events induced by angiotensin II (AngII) bindin g to the angiotensin II type 1 receptor resemble those evoked by platelet-d erived growth factor (PDGF) binding to the PDGF-beta receptor (PDGF beta-R) , We report here, in agreement with previous data, that AngII and PDGF-B-ch ain homodimer (PDGF-BB) stimulate tyrosine phosphorylation of the PDGF beta -R. Both AngII and PDGF-BB stimulated the phosphorylation of PDGF beta-R vi a the binding of tyrosine-phosphorylated Shc to PDGF beta-R, Both PDGF-BB a nd AngII-induced phosphorylation of the Shc PDGF beta-R complex was inhibit ed by antioxidants such as N-acetylcysteine and Tiron, but not by calcium c helation, However, transactivation of PDGF beta-R by AngII (measured by PDG F beta-R tyrosine phosphorylation) differed significantly from PDGF-BB. Evi dence to support different mechanisms of PDGF beta-R phosphorylation includ es differences in the time course of PDGFP-R phosphorylation, differing eff ects of inhibitors of the endogenous PDGF beta-R tyrosine kinase and Src fa mily tyrosine kinases, differing results when the PDGFP-R was directly immu noprecipitated (PDGF beta-R-antibody) versus coimmunoprecipitated (Shc-anti body), and cell fractionation studies that suggested that the Shc PDGF beta -R complexes phosphorylated by AngII and PDGF-BB were located in separate s ubcellular compartments. These studies are the first to suggest that transa ctivation of tyrosine kinase receptors by G protein-coupled receptors invol ves a unique pathway that regulates a population of tyrosine kinase recepto rs different from the endogenous tyrosine kinase ligand.