title: Angiotensin II-induced MAPK phosphorylation mediated by Ras and/or phospholipase C-dependent phosphorylations but not by protein kinase C phosphorylation in cultured rat vascular smooth muscle cells.
abstract: Angiotensin II (Ang II) induces a rapid increase in mitogen-activated protein kinase (MAPK) activity through the Ang II type 1 receptor in cultured rat vascular smooth muscle cells (VSMCs). In the present study, we examined the effects of the phospholipase C (PLC) inhibitor U73122, the protein kinase C (PKC) inhibitor GF109203X, and the Ras inhibitor farnesylthiosalicylic acid (FTS) on Ang II-induced activation of p42/p44 MAPKs in cultured VSMCs. Phosphorylation was shown using the Western blot technique with specific phospho-antibodies against MAPK proteins. The PLC inhibitor U73122 abolished the Ang II-induced MAPK activity, while the PKC inhibitor GF109203X only decreased it. There was also an inhibition observed with the Ras inhibitor, FTS on Ang II-induced MAPK activity. These data suggest that Ang II-induced MAPK phosphorylation through the Ang II type 1 receptor could be mediated by Ras and/or PLC-dependent phosphorylations but not by PKC phosphorylation.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Akdeniz University, Antalya, Turkey.
authors.forename: Arzu
authors.initials: A
authors.lastname: Cetin
authors.forename: O Hasan
authors.initials: OH
authors.lastname: Ozturk
authors.forename: Alper
authors.initials: A
authors.lastname: Tokay
authors.forename: Ferhat
authors.initials: F
authors.lastname: Akçit
authors.forename: Serkan
authors.initials: S
authors.lastname: Cağlar
authors.forename: Akin
authors.initials: A
authors.lastname: Yeşilkaya
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005204:Farnesol / Q000031:analogs & derivatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D012459:Salicylates / Q000494:pharmacology; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D004963:Estrenes; D007211:Indoles; D008301:Maleimides; D011760:Pyrrolidinones; D044140:Receptor, Angiotensin, Type 1; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D000804:Angiotensin II; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D005204:Farnesol; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D018631:ras Proteins; D019808:Losartan; C070515:bisindolylmaleimide I