Akt regulates thrombin-induced HSP27 phosphorylation in aortic smooth muscle cells: function at a point downstream from p38 MAP kinase.
We previously reported that p38 MAP kinase takes part in thrombin-induced HSP27 phosphorylation in aortic smooth muscle A10 cells. In the present study, we investigated whether Akt is involved in the phosphorylation of HSP27 and the role of adenylyl cyclase-cAMP system. Thrombin time-dependently induced the phosphorylation of heat shock protein 27 (HSP27) and Akt in aortic smooth muscle A10 cells. SB203580, a p38 MAP kinase inhibitor, significantly suppressed the thrombin-induced phosphorylation of Akt and the Akt inhibitor suppressed the phosphorylation of HSP27. Furthermore, the thrombin-induced phosphorylation of HSP27, p38 MAP kinase and Akt were decreased by dibutyryl-cAMP (DBcAMP). These results strongly suggest that Akt functions the thrombin-induced phosphorylation of HSP27 at a point downstream from p38 MAP kinase in aortic smooth muscle cells and the adenylyl cyclase-cAMP system is upstream regulator of the HSP27 phosphorylation in these cells.
Nakajima
Keiichi
K
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Hirade
Kouseki
K
Ishisaki
Akira
A
Matsuno
Hiroyuki
H
Suga
Hidetaka
H
Kanno
Yosuke
Y
Shu
En
E
Kitajima
Yasuo
Y
Katagiri
Yoshihiro
Y
Kozawa
Osamu
O
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000166:cytology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013917:Thrombin / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D006360:Heat-Shock Proteins; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D013917:Thrombin; D000262:Adenylyl Cyclases; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole; C093642:SB 203580