Involvement of CaM kinase II in gonadotropin-releasing hormone-induced activation of MAP kinase in cultured hypothalamic neurons.
Gonadotropin-releasing hormone (GnRH) is secreted from hypothalamic GnRH neurons. There is accumulating evidence that GnRH neurons have GnRH receptors and that the autocrine action of GnRH activates MAP kinase. In this study, we found that KN93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinases (CaM kinases), inhibited the GnRH-induced activation of MAP kinase in immortalized GnRH neurons (GT1-7 cells). Immunoblot analysis indicated that the CaM kinase IIdelta2 isoform (CaM kinase IIdelta2) and synapsin I were expressed in GT1-7 cells. GnRH treatment rapidly increased phosphorylation of synapsin I at serine 603, a specific phosphorylation site for CaM kinase II, suggesting that GnRH treatment rapidly activated CaM kinase IIdelta2. In addition, when we stably overexpressed CaM kinase IIdelta2 in GT1-7 cells, the activation of MAP kinase was strongly enhanced. These results suggest that CaM kinase IIdelta2 was involved in the GnRH-induced activation of MAP kinase in GT1-7 cells.
Yamanaka
Ayana
A
Department of Biochemistry, School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan.
Hiragami
Yukari
Y
Maeda
Noriko
N
Toku
Seikichi
S
Kawahara
Masahiro
M
Naito
Yasuhito
Y
Yamamoto
Hideyuki
H
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology*; D051379:Mice; D009474:Neurons / Q000201:enzymology*; D051381:Rats; D015398:Signal Transduction; D016704:Synapsins / Q000378:metabolism
D016704:Synapsins; D007987:Gonadotropin-Releasing Hormone; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases