このエントリーをはてなブックマークに追加
ID 25577
本文ファイル
著者
Sueyoshi, Noriyuki
Shigeri, Yasushi
Kameshita, Isamu
キーワード
Ca2+/calmodulin-dependent protein kinase
protein phosphatase
phosphorylation
dephosphorylation
deactivation
disease
pathogenesis
inhibitor
chemical screening
NDC
医学
抄録(英)
Multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) play pivotal roles in intracellular Ca2+ signaling pathways. There is growing evidence that CaMKs are involved in the pathogenic mechanisms underlying various human diseases. In this review, we begin by briefly summarizing our knowledge of the involvement of CaMKs in the pathogenesis of various diseases suggested to be caused by the dysfunction/dysregulation or aberrant expression of CaMKs. It is widely known that the activities of CaMKs are strictly regulated by protein phosphorylation /dephosphorylation of specific phosphorylation sites. Since phosphorylation status is balanced by protein kinases and protein phosphatases, the mechanism of dephosphorylation/deactivation of CaMKs, corresponding to their “switching off", is extremely important, as is the mechanism of phosphorylation/activation corresponding to their “switching on". Therefore, we focus on the regulation of multifunctional CaMKs by protein phosphatases. We summarize the current understanding of negative regulation of CaMKs by protein phosphatases. We also discuss the biochemical properties and physiological significance of a protein phosphatase that we designated as Ca2+ /calmodulin-dependent protein kinase phosphatase (CaMKP), and those of its homologue CaMKP-N. Pharmacological applications of CaMKP inhibitors are also discussed. These compounds may be useful not only for exploring the physiological functions of CaMKP/CaMKP-N, but also as novel chemotherapies for various diseases.
掲載誌名
British Journal of Pharmacology
154巻
4号
開始ページ
729
終了ページ
740
出版年月日
2008-05
出版者
Nature Publishing Group
ISSN
0007-1188
NCID
出版者DOI
PubMedID
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
Copyright (c) 2008 Nature Publishing Group
関連情報URL(IsVersionOf)
http://dx.doi.org/10.1038/bjp.2008.127
部局名
総合科学研究科