CaMキナーゼホスファターゼの構造と機能

カルモデュリン依存性プロテインキナーゼ（CaMK）は、高等動物の記憶や学習といった高次神経機能などにおいて重要な働きをするタンパク質リン酸化酵素である。CaMKI、II、IVはリン酸化を受けることにより、活性化されることが知られているが、その活性は、リン酸化酵素とは逆の脱リン酸化酵素（プロテインホスファターゼ）により負の制御を受けている。CaMKホスファターゼ（CaMKP）は、CaMKに特異的に働くプロテインホスファターゼとして、1997年に我々によって最初に報告された酵素である。その後、CaMKPと性質は似ているが、脳に豊富に存在し、細胞の中では核に存在するCaMKP-Nを報告した。これらのホスファターゼの酵素学的な性質については、その後様々な解析を行ってきたが、生理的な機能についての解析を現在進めているところである。これらの酵素の詳しい内容については、日本語の総説があるので、そちらを参照していただきたい。

茂里　康、石田敦彦、末吉紀行、亀下　勇
"Ca2+/カルモジュリン依存性プロテインキナーゼによるシグナル伝達　ースイッチオン/オフの制御機構と疾患とのかかわりー"
蛋白質核酸酵素 53, 1360-1367(2008)

末吉紀行、二村貴樹、亀下　勇
“カルモジュリンキナーゼに特異的に作用するホスファターゼ”
バイオサイエンスとインダストリー　65, 244-245 (2007)

末吉紀行、石田敦彦、亀下　勇
“カルモデュリン依存性プロテインキナーゼを制御するプロテインホスファターゼ”
生化学　77, 1317-1326 (2005)　

Ozaki, H., Katoh, T., Nakagawa, R., Ishihara, Y., Sueyoshi, N., Kameshita, I., Taniguchi, T., Hirano, T., Yamazaki, T., Ishida, A.
"Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) interacts with neurofilament L and inhibits its filament association."
Biochem. Biophys. Res. Commun. in press (2016)

Onouchi, T., Kishino-Kaneko, Y., Kameshita, I., Ishida, A., Sueyoshi, N.
"Regulation of Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) by protocadherin-gC5 (Pcdh-gC5)."
Arch. Biochem. Biophys. 585, 109-120 (2015)

Ishida, A., Tsumura, K., Oue, M., Takenaka, Y., Shigeri, Y., Goshima, N., Ishihara, Y., Hirano, T., Baba, H., Sueyoshi, N., Kameshita, I., Yamazaki T.
"An active C-terminally truncated form of Ca2+/calmodulin-dependent protein kinase phosphatase-N (CaMKP-N/PPM1E)."
Biomed. Res. Int. doi: 10.1155/2013/134813 (2013)

Baba, H., Sueyoshi, N., Shigeri, Y., Ishida, A., Kameshita, I.
"Regulation of Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP) by oxidation/reduction at Cys-359."
Arch. Biochem. Biophys. 526, 9-15 (2012)

Onouchi, T., Sueyoshi, N., Ishida, A., Kameshita, I.
"Phosphorylation and activation of nuclear Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP-N/PPM1E) by Ca2+/calmodulin-dependent protein kinase I (CaMKI)."
Biochem. Biophys. Res. Commun. 422, 703-709 (2012)

Sueyoshi, N., Nimura, T., Onouchi, T., Baba, H., Takenaka, S., Ishida, A., Kameshita, I.
"Functional processing of nuclear Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP-N): evidence for a critical role of proteolytic processing in the regulation of its catalytic activity, subcellular localization and substrate targeting in vivo."
Arch. Biochem. Biophys. 517, 43-52 (2012)

Sueyoshi, N., Nimura, T., Ishida, A., Taniguchi, T., Yoshimura, Y., Ito, M., Shigeri, Y., Kameshita, I.
"Calcium/calmodulin-dependent protein kinase phosphatase (CaMKP) is indispensable for normal embryogenesis in zebrafish, Danio rerio."
Arch. Biochem. Biophys. 488, 48-59 (2009)

Ishida, A., Sueyoshi, N., Shigeri, Y., Kameshita, I.
"Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases : physiological and pharmacological significance of protein phosphatases."

Br. J. Pharmacol. 154, 729-740 (2008)

Sueyoshi, N., Takao, T., Nimura, T., Sugiyama, Y., Numano, T., Shigeri, Y., Taniguchi, T., Kameshita, I., and Ishida, A.
“Inhibitors of the Ca2+/calmodulin-dependent protein kinase phosphatase family (CaMKP and CaMKP-N)”
Biochem. Biophys. Res. Commun. 363, 715-721 (2007)

Nimura, T., Sueyoshi, N., Ishida, A., Yoshimura, Y., Ito, M., Tokumitsu, H., Shigeri, Y., Nozaki, N., and Kameshita, I.
“Knockdown of nuclear Ca2+/calmodulin-dependent protein kinase phosphatase causes developmental abnormalities in zebrafish”
Arch. Biochem. Biophys. 457, 205-216 (2007)

Tada, Y., Nimura, T., Seuyoshi, N., Ishida,A., and Kameshita, I.
“Mutational analysis of Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP)”
Arch. Biochem. Biophys. 452, 174-185 (2006)　

Ishida, A., Tada, Y., Nimura, T., Sueyoshi, N., Katoh, T., Takeuchi, M., Fujisawa, H., Taniguchi, T., and Kameshita, T.
“Identification of major Ca2+/calmodulin-dependent protein kinase phosphatase-binding protein in brain: biochemical analysis of the interaction”
Arch. Biochem. Biophys. 435, 134-146 (2005)

Ishida, A., Shigeri, Y., Taniguchi, T., and Kameshita, I.
“Protein phosphatase that regulate multifunctional Ca2+/calmodulin-dependent protein kinases: from biochemistry to pharmacology”
Pharm. Ther. 100, 291-305 (2003)

Ishida, A., Kameshita, I., Kitani, T., Okuno, S., Takeuchi, M., Fujisawa, H.
“Stimulation of Ca2+/Calmodulin-dependent Protein Kinase Phosphatase by Polycations”
Arch. Biochem. Biophys. 408, 122-131 (2002)

Takeuchi, M., Ishida, A., Kameshita, I., Kitani, T., Okuno, S., Fujisawa, H.
“Identification and Characterization of CaMKP-N, Nuclear Calmodulin-dependent Protein Kinase Phosphatase”
J. Biochem. 130, 833-840 (2001)

Ishida, A., Kameshita, I., Okuno, S., Kitani, T., Yumoto, N., Fujisawa, H.
“Substrate Specificities of Calmodulin-dependent Protein Kinase Phosphatase”
J. Biochem. 129, 745-753 (2001)

Kameshita, I., Ishida, A., Fujisawa, H.
“Phosphorylation and Activation of Ca2+/Calmodulin-dependent Protein Kinase Phosphatase by Ca2+/Calmodulin-dependent Protein Kinase II”
FEBS Lett. 456, 249-252 (1999)

Kitani, T., Ishida, A., Okuno, S., Takeuchi, M., Kameshita, I., Fujisawa, H.
“Molecular Cloning of Ca2+/Calmodulin-dependent Protein Kinase Phosphatase”
J. Biochem. 125, 1022-1028 (1999)

Ishida, A., Okuno, S., Kitani, T., Kameshita, I., and Fujisawa, H.
“Regulation of multifunctional Ca2+/calmodulin-dependent protein kinases by Ca2+/calmodulin-dependent protein kinase phosphatase”
Biochem. Biophys. Res. Commun. 253, 159-163 (1998)

Ishida, A., Kameshita, I., and Fujisawa, H.
“Novel protein phosphatase that dephosphorylates and regulates Ca2+/calmodulin-dependent protein kinase II”
J. Biol. Chem. 273, 1904-1910 (1998)

Ishida, A., Kameshita, I., and Fujisawa, H.
“Assay of protein phosphatase activities with phosphopeptide-magnetic particle conjugates”
Anal. Biochem. 254, 152-155 (1997)

Kameshita, I., Ishida, A., and Fujisawa, H.
“Detection of protein phosphatase activities in sodium dodecyl sulfate-polyacrylamide gel using peptide substrates”
Anal. Biochem. 245, 149-153 (1997)