RGD Reference Report - Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases. - Rat Genome Database

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

Authors: Ishida, A  Sueyoshi, N  Shigeri, Y  Kameshita, I 
Citation: Ishida A, etal., Br J Pharmacol. 2008 Jun;154(4):729-40. doi: 10.1038/bjp.2008.127. Epub 2008 May 5.
RGD ID: 7241020
Pubmed: PMID:18454172   (View Abstract at PubMed)
PMCID: PMC2439855   (View Article at PubMed Central)
DOI: DOI:10.1038/bjp.2008.127   (Journal Full-text)

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.

Objects Annotated

Genes (Rattus norvegicus)
Ppm1e  (protein phosphatase, Mg2+/Mn2+ dependent, 1E)
Ppm1f  (protein phosphatase, Mg2+/Mn2+ dependent, 1F)
Ppp1cc  (protein phosphatase 1 catalytic subunit gamma)
Ppp2ca  (protein phosphatase 2 catalytic subunit alpha)

Genes (Mus musculus)
Ppm1e  (protein phosphatase 1E (PP2C domain containing))
Ppm1f  (protein phosphatase 1F (PP2C domain containing))
Ppp1cc  (protein phosphatase 1 catalytic subunit gamma)
Ppp2ca  (protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform)

Genes (Homo sapiens)
PPM1E  (protein phosphatase, Mg2+/Mn2+ dependent 1E)
PPM1F  (protein phosphatase, Mg2+/Mn2+ dependent 1F)
PPP1CC  (protein phosphatase 1 catalytic subunit gamma)
PPP2CA  (protein phosphatase 2 catalytic subunit alpha)


Additional Information