title: 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.
authors.affiliation: Upjohn Laboratories, Kalamazoo, Michigan 49001, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Linseman
authors.forename: C W
authors.initials: CW
authors.lastname: Benjamin
authors.forename: D A
authors.initials: DA
authors.lastname: Jones
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D017077:Culture Media, Conditioned; D051380:GRB2 Adaptor Protein; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D017077:Culture Media, Conditioned; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495950:Grb2 protein, rat; D007093:Imidazoles; D011506:Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013777:Tetrazoles; D000804:Angiotensin II; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D019204:GTP-Binding Proteins; D019808:Losartan