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ID 25577
file
creator
Sueyoshi, Noriyuki
Shigeri, Yasushi
Kameshita, Isamu
subject
Ca2+/calmodulin-dependent protein kinase
protein phosphatase
phosphorylation
dephosphorylation
deactivation
disease
pathogenesis
inhibitor
chemical screening
NDC
Medical sciences
abstract
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.
journal title
British Journal of Pharmacology
volume
Volume 154
issue
Issue 4
start page
729
end page
740
date of issued
2008-05
publisher
Nature Publishing Group
issn
0007-1188
ncid
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2008 Nature Publishing Group
relation is version of URL
http://dx.doi.org/10.1038/bjp.2008.127
department
Graduate School of Integrated Arts and Sciences