Prostaglandin D2 induces the phosphorylation of HSP27 in osteoblasts: function of the MAP kinase superfamily.
We previously reported that prostaglandin D(2) (PGD(2)) stimulates the induction of heat shock protein 27 (HSP27) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether PGD(2) stimulates the phosphorylation of HSP27 in MC3T3-E1 cells exposed to heat shock. In the cultured MC3T3-E1 cells, PGD(2) markedly stimulated the phosphorylation of HSP27 at Ser-15 and Ser-85 in a time-dependent manner. Among the mitogen-activated protein (MAP) kinase superfamily, p44/p42 MAP kinase and p38 MAP kinase were phosphorylated by PGD(2) which had little effect on the phosphorylation of stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK). The PGD(2)-induced phosphorylation of HSP27 was attenuated by PD169316, an inhibitor of p38 MAP kinase or PD98059, a MEK inhibitor. SP600125, a SAPK/JNK inhibitor did not affect the HSP27 phosphorylation. In addition, PD169316 suppressed the PGD(2)-induced phosphorylation of MAPKAP kinase 2. These results strongly suggest that PGD(2) stimulates HSP27 phosphorylation via p44/p42 MAP kinase and p38 MAP kinase but not SAPK/JNK in osteoblasts.
Takai
Shinji
S
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Tokuda
Haruhiko
H
Yoshida
Minoru
M
Yasuda
Eisuke
E
Matsushima-Nishiwaki
Rie
R
Harada
Atsushi
A
Kato
Kanefusa
K
Kozawa
Osamu
O
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000145:classification / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D000873:Anthracenes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006360:Heat-Shock Proteins; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C432165:pyrazolanthrone; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one