Angiotensin II controls p21ras activity via pp60c-src.
Angiotensin II is the major effector peptide of the renin-angiotensin system, and it exerts its physiologic functions via a G protein-coupled cell surface receptor called AT1. We found that in rat aortic smooth muscle cells, angiotensin II stimulated the formation of Ras-GTP, Ras-Raf-1 complex formation, and the tyrosine phosphorylation of two important Ras GTPase-activating proteins (GAPs), p120 Ras-GAP and p190 Rho-GAP. Electroporation of anti-pp60c-src antibody into cultured, adherent smooth muscle cells blocked the angiotensin II stimulation of Ras-GAP and Rho-GAP tyrosine phosphorylation. In contrast electroporation of antibodies against c-Yes or c-Fyn had no effect. Anti-pp60c-src antibody also blocked angiotensin II-stimulated Ras activation and Ras-Raf-1 complex formation. These data strongly suggest that a G protein-coupled receptor such as the AT1 receptor can activate the Ras protein cascade via the tyrosine kinase pp60c-src.
Schieffer
B
B
Department of Pathology Center for Molecular and Cellular Signaling, Emory University, Atlanta, Georgia 30322, USA.
Paxton
W G
WG
Chai
Q
Q
Marrero
M B
MB
Bernstein
K E
KE
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006801:Humans; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology*; D015398:Signal Transduction; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011945:Receptors, Angiotensin; D020703:ras GTPase-Activating Proteins; D000804:Angiotensin II; D019000:Phosphotyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D019204:GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)