Angiotensin II type 1 receptor-mediated activation of Ras in cultured rat vascular smooth muscle cells.
Angiotensin II (ANG II), a potent growth-promoting factor of vascular smooth muscle cells (VSMC), induces activation of mitogen-activated protein (MAP) kinases and subsequent expression of the c-fos protooncogene in VSMC. However, it remains obscure whether ANG II induces activation of the ras protooncogene product (Ras), and if it does, whether Ras is involved in signaling from the ANG II receptor to the MAP kinase pathway in VSMC. In cultured VSMC, ANG II activated Ras comparably to epidermal growth factor. ANG II-induced Ras activation was detectable within 1 min and maximal at 2-5 min. The ANG II type 1 (AT1) receptor antagonist, CV-11974, completely inhibited this reaction. Pertussis toxin treatment of VSMC inhibited ANG II-induced Ras activation by approximately 70% but had no effect on ANG II-induced MAP kinase activation and c-fos expression. These results indicate that ANG II activates Ras via AT1 receptors, which are predominantly linked to a G protein of the Gi subfamily in VSMC1 and suggest that Ras activation may not be a prerequisite for ANG II-induced MAP kinase activation and c-fos expression in this cell type.
Okuda
M
M
Department of Internal Medicine (First Division), Kobe University School of Medicine, Japan.
Kawahara
Y
Y
Yokoyama
M
M
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D011905:Genes, ras; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D037342:Pertussis Toxin; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016760:Proto-Oncogene Proteins c-fos; D011945:Receptors, Angiotensin; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D037342:Pertussis Toxin; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins