Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases

British Journal of Pharmacology 154 巻 4 号 729-740 頁 2008-05 発行
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タイトル ( eng )
Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases
作成者
Sueyoshi Noriyuki
Shigeri Yasushi
Kameshita Isamu
収録物名
British Journal of Pharmacology
154
4
開始ページ 729
終了ページ 740
抄録
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.
著者キーワード
Ca2+/calmodulin-dependent protein kinase
protein phosphatase
phosphorylation
dephosphorylation
deactivation
disease
pathogenesis
inhibitor
chemical screening
NDC分類
医学 [ 490 ]
言語
英語
資源タイプ 学術雑誌論文
出版者
Nature Publishing Group
発行日 2008-05
権利情報
Copyright (c) 2008 Nature Publishing Group
出版タイプ Author’s Original(十分な品質であるとして、著者から正式な査読に提出される版)
アクセス権 オープンアクセス
収録物識別子
[ISSN] 0007-1188
[DOI] 10.1038/bjp.2008.127
[NCID] AA00574810
[PMID] 18454172
[DOI] http://dx.doi.org/10.1038/bjp.2008.127 ~の異版である