Regulation of CaMKKbeta/AMPK signaling and drug development
Project/Area Number |
18K06113
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 43030:Functional biochemistry-related
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Research Institution | Okayama University |
Principal Investigator |
Tokumitsu Hiroshi 岡山大学, ヘルスシステム統合科学研究科, 教授 (20237077)
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Co-Investigator(Kenkyū-buntansha) |
曲 正樹 岡山大学, ヘルスシステム統合科学研究科, 助教 (50359882)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | CaMKK / タンパク質リン酸化反応 / タンパク質脱リン酸化反応 / 阻害剤 / TIM-063 / TIM-062 / Ca2+シグナル伝達 / タンパク質リン酸化酵素 / calmodulin / CaMKKβ / PP2A / PP1 / PKA / HeLa細胞 / cAMP / AMPK / イソプロテレノール / 酵素阻害剤 / シグナル伝達 / 細胞内カルシウム情報伝達 |
Outline of Final Research Achievements |
We have obtained the results regarding CaMKK-mediated intracellular signal transduction as follows; (1) CaMKKβ is phosphorylated at Thr144 in HeLa cells upon stimulation with isoproterenol, indicating the regulatory phosphorylation of CaMKKβ by cAMP-mediated signaling. (2) CaMKKβ is also rapidly dephosphorylated in the cells suggesting the dynamic regulation of CaMKKβ through phosphorylation/dephosphorylation. (3) We have succeeded to develop a novel CaMKK inhibitor (TIM-063) and an inactive analogue (TIM-062) which could be useful for evaluating the physiological roles of CaMKK-mediated signaling pathways.
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Academic Significance and Societal Importance of the Research Achievements |
Ca2+/Calmodulin(CaM)依存性プロテインキナーゼ活性化キナーゼ(CaMKK)は、CaMキナーゼⅠやCaMキナーゼⅣ、5’-AMP活性化キナーゼ(AMPK)をリン酸化依存的に活性化し、遺伝子発現や神経発生、代謝調節に至る多様な細胞内Ca2+に応答した生理機能を調節するとともに、前立腺がん増殖などの疾患との関連も示唆されている。本研究により、CaMKKの詳細な細胞内調節機構を解明し、正常および病態におけるCaMKKの役割の一端を解明するとともに、治療薬の開発を目指した新たなCaMKK阻害剤の創製に成功した。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Development and Characterization of Novel Molecular Probes for Ca2+/Calmodulin-Dependent Protein Kinase Kinase, Derived from STO-609.2020
Author(s)
Ohtsuka S, Ozeki Y, Fujiwara M, Miyagawa T, Kanayama N, Magari M, Hatano N, Suizu F, Ishikawa T, and Tokumitsu H.
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Journal Title
Biochemistry
Volume: 59(17)
Issue: 17
Pages: 1701-1710
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Book] Methods Mol Biol.2019
Author(s)
Sakane K, Yamaguchi F, Tsuchiya M, Kondo R, Kanayama N, Magari M, Hatano N, Kobayashi R, Tokumitsu H.
Total Pages
11
Publisher
Humana Press, New York, NY
ISBN
9781493990290
Related Report
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