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Regulation of gene expression mediated by Ca^<2+>/calmodulin-dependent protein kinase cascade

Research Project

Project/Area Number 12680637
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionKagawa Medical University

Principal Investigator

TOKUMITSU Hiroshi  Kagawa Medical University, Medicine, Associate Professor, 医学部, 助教授 (20237077)

Co-Investigator(Kenkyū-buntansha) KIMURA Yoshishige  Helix Research Institute, 3rd Department, Researcher, 第3研究部門, 研究員
KOBAYASHI Ryoji  Kagawa Medical University, Medicine, Professor, 医学部, 教授 (00020917)
MURAO Koji  Kagawa Medical University, University Hospital, Assistant Professor, 医学部・附属病院, 助手 (20291982)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsIntracellalr Calcium / Calmodulin / CaM-KK / Sgnal Transduction / Protein Kinase cascade / CREB / C.elegans / CaM-kinase / 細胞内カルシウム
Research Abstract

Ca^<2+>/calmodulin-dependent protein kinases (CaM-Ks) constitute a diverse group of enzymes, which are involved in many cellular responses mediated by an increase in the concentration of intracellular calcium. Previous studies have demonstrated that two multifunctionla CaM-kinases, CaM-KI and IV, are activated byphosphorylation of an activation loop Thr residue by an upstream CaM-kinase (CaM-KK) resulting in a large increase in catalytic efficiency. In this study, we have found that Ile441 in CaM-KKα is essential for the autoinhibition of CaM-KK and the binding orientation of CaM to CaM-KKα is not critical for relief of the autoinhibition. The unique binding orientation of CaM to CaM-KKα which was originally discovered using NMR analysis, was also confirmed with C.elegans CaM-KK by using X-ray crystallography. In contrast to CaM-KKα, CaM-KKβ-isoform has shown to exhibit enhanced Ca^<2+>/CaM-independent activity which is due to the second regulatory domain (residues 129-151) located in N-terminal of the catalytic domain. This domain inhibits the autoinhibition of CaM-KKβ resulting in generation of its autonomous activity. We also have generated C.elegans carrying CRE-GFP reporter gene and cloned C.elegans CREB. C.elegans CREB-mediated gene expression was induced by C.elegans CaM-K cascade (CaM-KK/CaM-KI) in transfected cells. In living worm, GFP-expression was induced by overexpression of C.elegans CaM-KI 1-295 (constitutively active mutant) in some neurons, which was not observed in CREB-deficient worm. This indicates that CaM-K cascade mediats CREB-dependent transcriptional activation is conserved in C.elegans.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] 徳光 浩: "Regulatory Mechanism of Ca^<2+>/Calmodulin-Dependent Protein Kinase Kinase"The Journal of Biological Chemistry. 275. 20090-20095 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 徳光 浩: "Differential Regulatory Mechanism of Ca^<2+>/Calmodulin-Dependent Protein Kinase Kinase"Biochemistry. 40. 13925-13932 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 黒河博文: "Target-induced Conformational Adaptation of Calmodulin Revealed by the Crystal Structure of a Complex with Nematode Ca^<2+>/Calmodulin-pependent Protein Kinase Kinase"Journal of Molecular Biology. 312. 59-68 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiroshi Tokumitsu et al.: "Regulatory Mechanism of Ca^<2+>/Calmodulin-dependent Protein Kinase Kinase"The Journal of Biological Chemistry. 275. 20090-20095 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hirofumi Korokawa et al.: "Target-induced Conformational Adaptation of Calmodulin Revealed by the Crystal Structure of a Complex with Nematode Ca^<2+>/Calmodulin-dependent Protein Kinase Kinase Peptide"Jouranal of Molecular Biology. 312. 59-68 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiroshi Tokumitsu et al.: "Differential Regulatory Mechanism of Ca^<2+>/Calmodulin-dependent Protein Kinase Kinase Isoforms"Biochemistry. 40. 13925-13932 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tokumitsu, H.: "Differential Regulatory Mechanism of Ca^<2+>/Calmodulin-Dependent Protein Kinase Kinase"Biochemistry. 40・46. 13925-13932 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kurokawa, H.: "Target-induced Conformational Adaptation of Calmodulin Revealed by the Crystal Structure of a Complex with Nematode Ca^<2+>/Calmodulin-Dependent Protein Kinase Kinase"Journal of Molecular Biology. 312. 59-68 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 徳光浩,村松正明,伊倉光彦,小林良二: "Regulatory Mechanism of Ca^<2+>/Calmodulin-dependent Protein Kinase Kinase"The Journal of Biological Chemistry. 275・26. 20090-20095 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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