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Role of calmodulin kinases on the regulation of Ca^<2+> signaling of central nervous systems

Research Project

Project/Area Number 10470484
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionThe University of Tokushima

Principal Investigator

YAMAUCHI Takashi  The University of Tokushima, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90041813)

Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsCalmodulin / CaMKII / Ca^<2+> / phosphorylation / protein kinase / gene expression / neurite outgrowth / neural differentiation / タンパク質リン酸 / キナーゼ / リン酸化 / P19細胞 / CaM Kinase II / シナプス可塑性 / Ca^<2+> / カルモデュリン依存性プロテインキナーゼ / 情報伝達 / シナプス後肥原 / トランスロケーション / 可塑性 / 神経突起
Research Abstract

Neuronal Ca^<2+> /calmodulin-dependent protein kinase II (CaM kinase II) regulates important neuronal functions, including neurotransmitter synthesis and neurotransmitter release, modulation of ion channel activity, synaptic plasticity, and gene expression. The following results were obtained in this study; 1. when CaM kinase II was introduced in neuronal cells, neurite outgrowth was stimulated, indicating that CaM kinase II played a role stimulation of neurite outgrowth; 2. Ca^<2+> independent activity of the kinase autophosphorylated at Thr-286 involved in neurite outgrowth; 3. more than 28 protein substrates of CaM kinase II were found in the postsynaptic density (PSD), and almost all of these proteins were identified by protein sequencing and mass spectrometry; 4. when the developmental change of the kinase was investigated during the neural differentiation of cultured cells, it was found that CaM kinase II was upregulated during the neuronal differentiation; 5. cell type distinctive changes of splicing pattern of δ isoform were found not only during development of rat brain tissue, but also during differentiation of cultured neuronal cells, indicating that alternatively spliced variants of δ isoform of CaM kinase II were expressed during neural differentiation; 6. when we used the deletion mutants for β-specific insertions to explore the difference between α and β CaM kinase II in enzymatic properties, it was found that β specific insertion of β CaM kinase II played an important role in the cellular distribution of the kinase; 7 The gene encoding the β isoform of rat Ca^<2+>/calmodulin-dependent protein kinase II was cloned, and its structure and exon-intron organization were determined; 8. When the promoter activity of the gene was analyzed using nueronal and non-neuronal cells, neuronal cell type-specific promoter activity was found in the 5'-upstream region of the gene.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Yoshimura, Y., et al.: "Investigation of protein substrates of Ca2+-calmodulin----"Molecular Brain Research. 81. 118-128 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Donai, H., et al.: "Induction and alternative splicing of δ isoform of Ca2+/---"Molecular Brain Research. 85. 189-199 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mima, K., et al.: "Characterization of 5' flanking region of α isoform of rat Ca2+/calmodulin-dependent protein kinase II gene---"Nenosci. Lett.. 307. 117-121 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Donai, H., et al.: "Genomic organization and neuronal cell type specific promoter activity of β isoform of Ca2+/calmodulin-dependent---"Mol. Brain Res.. 94. 35-47 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Urushihara, M., et al.: "Role of β isoform-specific insertions of Ca2+/calmodulin-dependent protein kinase"Eur. J. Biochem.. 268. 4802-4808 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sogawa, Y., et al.: "Investigation of the Ca2+-independent form of Ca2+/calmodulin-dependent protein kinase II in neurite outgrowth"Brain Res Protocols. 8. 159-169 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamauchi,T. et al.: "Phosphorylation-dependent reversible transloeation of Ca2+/calmodulin-dependent protein kinase II to the postsynaptic densities"Life Sci. 62. 1617-1621 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimura,Y. et al.: "Protein phosphatase 1 is involved in the dissociation of Ca2+/calmodulin-dependent protein kinase II from postsynaptic densities."FEBS Lett. 446. 239-242 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshimura,Y. et al.: "Investigation of protein substrates of Ca2+/calmodulin-dependent protein kinase II translocated to the postsynaptic density"Mol. Brain Res. 81. 118-128 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sogawa,Y. et al.: "Ca2+-independent activity of Ca2+/calmodulin-dependent protein kinase II involved in stimulation of neurite outgrowth in neuroblastoma cells"Brain Res. 881. 165-175 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Donai,H. et al.: "Involvement of Ca2+/calmodulin-dependent protein kinase II in neurite outgrowth induced by CAMP and serum deprivation in a CNS cell lints, CAD, derived from rat brain"Neurosci. Lett. 293. 111-114 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Doani,H. et al.: "Induction and alternative Splicing of δ isoform of Ca2+/calmodulin-dependent protein kinase II during neural differentiation of P19 embryonal carcinoma cells and during brain development"Mol. Brain Res. 85. 189-199 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mima,K. et al.: "Characterization of 5' flanking region of α isoform of rat Ca2+/calmodulin-dependent protein kinase II gene and neuronal cell type specific promoter activity"Neuosci. Lett. 307. 117-121 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Donai,H. et al.: "Genomic organization and neuronal cell type specific promoter activity of β isoform of Ca2+/calmodulin-dependent protein kinase II of rat brain"Mol. Brain Res. 94. 35-47 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Urushihara,M. et al.: "Role of β isoform-specific insertions of Ca2+/calmodulin-dependent protein kinase II"Eur. J. Biochem. 268. 4802-4808 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sogawa,Y. et al.: "Investigation of the Ca2+-independent form of Ca2+/calmodulin-dependent protein kinase n in neurite outgrowth"Brain Res Protocols. 8. 159-169 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mima, K., et al.: "Characterization of 5' flanking region of α isoform of rat Ca2+/calmodulin-dependent protein kinase II gene---"Neuosci. Lett.. 307. 117-121 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Donai, H., et al.: "Genomic organization and neuronal cell type specific promoter activity of β isoform of Ca2+/calmodulin-dependent---"Mol. Brain Res.. 94. 35-47 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Urushihara, M., et al.: "Role of β isoform-specific insertions of Ca2+/calmodulin-deendent protein kinase II."Eur. J. Biochem.. 268. 4802-4808 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sogawa, Y., et al.: "Investigation of the Ca2+-independent form of Ca2+/calmodulin-dependent protein kinase II in neurite outgrowth."Brain Res Protocols. 8. 159-169 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sogawa,Y., et al.: "Ca^<2+>-independent activity of Ca^<2+>/calmodulin-dependent-"Brain Reserach. 881. 165-175 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshimura,Y., et al.: "Investigation of protein substrates of Ca2+-calmodulin-"Molecular Brain Research. 81. 118-128 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Donai,H., et al.: "Induction and alternative splicing of δ isoform of Ca2+/ -"Molecular Brain Research. 85. 189-199 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Donai,H., et al.: "Involvement of Ca^<2+>/calmodulin-dependent protein kinase-"Neuroscience Letters. 293. 111-114 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshimura,Y.et al: "Protein phosphatase 1 is involved in ・・・"FEBS Lett. 446. 239-242 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujii,M.et al.: "Generation of immortalized murine forebrain cell lines ....." Biol.pharm.Bull.21. 210-213 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamauchi,T.et al.: "Neurite outgrowth of neuroblastoma cells overexpressing ...." Brain Res.Protocols. 2. 250-258 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ochiishi,T.et al.: "Regional differences between the immunohistochemical ...." Brain Res.790. 129-140 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamauchi,T.et al.: "Phosphorylation-dependent reversible translocation ....." Life Sci.62. 1617-1621 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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