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Regulation mechanisms of LIM-kinase-induced actin cytoskeletal reorganization

Research Project

Project/Area Number 11480213
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionTohoku University

Principal Investigator

MIZUNO Kensaku  Tohoku University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (70128396)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2000: ¥5,700,000 (Direct Cost: ¥5,700,000)
KeywordsLIM-kinase / LIMK / actin cytoskeleton / Rho / Rac / neurite outgrowth / TESK / コフィリン / インテグリン / LIMドメイン / プロテインキナーゼ / Rhoキナーゼ
Research Abstract

Actin cytoskeletal reorganization plays an important role in cell motility, adhesion, morphology, and cytokinesis. The aim of this project is to elucidate the regulation mechanisms of LIM-kinase (LIMK)-induced actin cytoskeletal reorganization. We have obtained following results.
1. The LIM domains of LIMK negatively regulates the kinase activity by directly interacting with the protein kinase domain.
2. LIMK1 and LIMK2 are activated by Rho-associated kinase, by phosphorylation of Thr-508 in LIMK1 and Thr-505 in LIMK2.
3. TESK1 phosphorylates cofilin at Ser-3 and induces actin reorganization, and these activity are regulated by integrin-mediated signaling.
4. We have identified a Drosophila LIM-kinase and found that it phosphorylates cofilin and induces actin reorganization.
5. The LIMK-cofilin signaling pathway plays a role in determining axon outgrowth in cerebeller granule neurons and in semaphorin 3A-induced neurite collapse in dorsal root ganglion neurons.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Maekawa,M., et al.: "Signaling from Rho to the actin cytoskeleton through protein kinases POCK and LIM-kinase."Science. 285. 895-898 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohashi,K., et al.: "Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine-508 within the activation loop."J.Biol.Chem.. 275. 3577-3582 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Bito,H., et al.: "A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons."Neuron. 26. 431-441 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Amano,T., et al.: "LIM-kinase 2 induces the formation of actin stress fibers, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase."Biochem.J.. 354. 149-159 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshima,J., et al.: "Cofilin phosphorylation by protein kinase TESK1 and its role in integrin-mediated actin remodeling."Mol.Biol.Cell. 12(4)(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aizawa,H., et al.: "Phosphorylation of cofilin by LIM kinase is necessary for semaphorin 3A-induced growth cone collapse."Nature Neurosci.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maekawa, M., et al.: "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase."Science. 285. 895-898 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohashi, K., et al.: "Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine-508 within the activation loop."J.Biol.Chem.. 275. 3577-3582 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Bito H., et al.: "A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons."Neuron. 26. 431-441 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Amano, T., et al.: "LIM-kinase 2 induces the formation of actin stress fibers, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase-catalyzed phosphorylation of threonine-505."Biochem.J.. 354. 149-159 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshima, J., et al.: "Cofilin phosphorylation by protein kinase TESK1 and its role in integrin-mediated actin remodeling."Mol.Biol.Cell. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aizawa, H., et al.: "Phosphorylation of cofilin by LIM kinase is necessary for semaphorin 3A-induced growth cone collapse."Nature Neurosci.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Ohashi, et al.: "A Drsophila homolog of LIM-kinase phosphorylates cofilin and induces actin cytoskeletal reorganization."Biochem.Biophys.Res.Commun.. 276. 1178-1185 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Bito, et al.: "A critical role for a Rho-associated kinase, p160ROCK, in determiningaxon outgrowth in mammalian CNS neurons."Neuron. 26. 431-441 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Amano, et al.: "LIM-kinase 2 induces formation of stress fibers, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase."Biochem.J.. 354. 149-159 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] J.Toshima, et al.: "Cofilin phosphorylation by protein kinase TESK1 and its role in integrinmediated actin reorganization and focal adhesion formation."Mol.Biol.Cell. 12(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Aizawa, et al.: "Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse."Nature Neurosci.. 4(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 十島二朗,水野健作: "基礎生化学実験法 第3巻 タンパク質 II.機能・動態解析法"東京化学同人(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Ohashi et al.: "Rho associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop"J. Biol. Chem.. 275巻5号. 3577-3582 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Maekawa et al.: "Signaling from Rho to the actin cytoskeleton through protein kinases Rock and LIM-kinase"Science. 285巻. 895-898 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Nagata et al.: "The N-terminal LIM domain negatively regulates the kinase activity of LIM-kinase 1"Biochem. J.. 343巻. 99-105 (1999)

    • Related Report
      1999 Annual Research Report

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

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