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Development and application of stress-signal transduction system as an assessment ofbiomaterials

Research Project

Project/Area Number 13557150
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Functional basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TAKEDA Kohsuke  Tokyo Medical and Dental University Graduate School, Research Associate, 大学院・医歯学総合研究科, 助手 (10313230)

Co-Investigator(Kenkyū-buntansha) ICHIJO Hidenori  The University of Tokyo Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (00242206)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2002: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2001: ¥6,900,000 (Direct Cost: ¥6,900,000)
KeywordsStress / Signal transduction / MAP kinase / Biomaterials
Research Abstract

Among the three MAP kinase cascades, two of them that converge on JNKs and p38 MAP kinases are preferentially activated by cytotoxic stresses such as UV radiation, X-ray, heat shock and osmotic shock, and by proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1. One of the important biological responses mediated through these stress-activated MAP kinase pathways appears to be the decision of cell fate by regulating apoptosis. In this research project, we intended to develop a novel, rapid and sensitive assessment system for various biomaterials by assaying the activation status of the stress-activated MAP kinase pathways. We first established the sensitive assay system for INK and p38 activation, and clearly showed that apoptosis signal^egulating kinase 1 (ASK1), which is known to regulate the JNK and p38 MAP kinase pathways, is required for oxidative stress-nduced activation of JNK and p38. We next established the sensitive assay system for ASK1 activation. We found that phosphorylation of Thr845 in the kinase domain of ASK1 is required for the activation of ASK1, and raised a polyclonal antibody that specifically recognized the activation status of Thr 845 of ASK 1. This anti-phospho-ASKl antibody could detect the activation state of ASK1 with much higher sensitivity than the conventional "in vitro kinase assay". By the various biochemical analyzes using this antibody and the further investigation of ASKl-deficient mice, we have found that ASK1 is necessary for not only oxidative stress- but also ER stress-induced apoptosis, suggesting that the ASK1-MAP kinase pathways is a common signal mediator of various kind of stressors. Thus, accurate and sensitive detection of the activation status of the ASK1-MAP kinase pathways appears to be useful for the development and application of our assessment system for various biomaterials.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Tobiume, K, et al.: "ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis"EMBO reports. 2. 222-228 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Geleziunas, R, et al.: "HIV-1 nef inhibits ASK1-dependent death signalingproviding a potential mechanism for protecting the infected host cell"Nature. 410. 834-838 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sawada, Y. et al.: "Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase"J. Cell Sci.. 114. 1221-1227 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yanagisawa, M. et al.: "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7"Genes Cells. 6. 1091-1099 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morita, K. et al.: "Negative feedback regulation of ASK1 by protein phophatase 5 (PP5) in response to oxidative stress"EMBO J.. 20. 6028-6036 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishitoh, H. et al.: "ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats"Genes Dev.. 16. 1345-1355 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoshita, S. et al.: "Phosphorylation and Inactivation of Mc1-1 by c-Jun N-terminal Kinase (JNK) in response to oxidative stress"J. Biol. Chem.. 277. 43730-43734 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuura, H. et al.: "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway : a new mode of regulation of the MAP kinase cascade"J. Biol. Chem.. 277. 40703-40709 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuzawa, A. et al.: "Physiological roles of ASK1-mediated signal transduction in oxidative stress-and endoplasmic reticulum stress-induced apoptosis : advanced findings from ASK1 knockout mice"Antioxid. Redox Signal. 4. 415-425 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda, K., Ichijo, H: "Neuronal p38 MAPK signalling : an emerging regulator of cell fate and function in the nervous system"Genes Cells. 7. 1099-1111 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tobiume, K. et al.: "Activation of apoptosis signal-regulating kinase 1 by the stress-induced activating phosphorylation of pre-formed oligomer"J. Cell. Physiol.. 191. 1091-1099 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuranaga, E. et al.: "Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila"Nat. Cell Biol.. 4. 705-710 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tobiume, K. et al.,: "ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis"EMBO reports. 2. 222-228 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Geleziunas, R. et al.,: "HIV-1 nef inhibits ASK 1-dependent death signalingproviding a potential mechanism for protecting the infected host cell"Nature. 410. 834-838 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sawada, Y. et al.,: "Rapl is involved in cell stretching modulation of p38 but not ERK or JNK MAP Mnase"J. Cell Sci.. 114. 1221-1227 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yanagisawa, M., et al.,: "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7"Genes Cells. 6. 1091-1099 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morita, K. et al.,: "Negative feedback regulation of ASK1 by protein phophatase 5(PP5) in response to oxidative stress"EMBO J.. 20. 6028-6036 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishitoh, H. et al.,: "ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats"Genes Dev.. 16. 1345-1355 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoshita, S. etal.,: "Phosphorylation and Inactivation of Mcl-1 by c-Jun N-terminal Kinase (JNK) in response to oxidative stress"J. Biol. Chem.,. 277. 43730-43734 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuura, H. etal.,: "Phbsphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway: a new mode of regulation of the MAP kinase cascade"J. Biol. Chem.,. 277. 40703-40709 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuzawa, A. et al.: "Physiological roles of ASK1- mediated signal transduction in oxidative stress- and endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1 knockout mice"Antioxid. Redox Signal.. 4. 415-425 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda, K. et al.: "Neuronal p38 MAPK.signalling: an emerging regulator of cell fate and function in the nervous system"Genes Cells. 7. 1099-1111 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tobiume, K. et al.: "Activation of apoptosis signal regulating kinase 1 by the stress4nduced activating phosphorylation of pre-formed oligomcr"J. Cell. Physiol.. 191. 95-104 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuranaga, E. et al.: "Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila"Nat.Cell Biol.. 4. 705-710 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuzawa, A. et al.: "Physiological roles of ASK1-mediated signal transduction in oxidativc stress-and endolasmic reticulum stress-induced apoptosis : advanced findings from ASK1 knockout mice."Antioxidants and Redox Signal. 4. 415-425 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishitoh, H. et al.: "ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats"Genes Dev.. 16. 1345-1355 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuura, H. et al.: "Phoshorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway : a new mode of regulation of the MAP kinase cascade"J. Biol. Chem.. 277. 40703-40709 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoshita, S. et al.: "Phosphorylation and Inactivation of Mcl-1 by c-Jun N-terminal Kinase (JNK) in response to oxidative stress"J. Biol. Chem.. 277. 43730-43734 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeda, K. et al.: "Neuronal p38 MAPK signalling : an emerging regulator of cell fate and function in the nervous system"Genes Cells. 7. 1099-1111 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuranaga, E. et al.: "Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila"Nat. Cell Biol.. 4. 705-710 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Geleziunas, R. et al.: "HIV-1 ncf inhibits ASK1-dependent death signalingproviding a potential mechanism for protecting the infected host cell"Nature. 410. 834-838 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sawada, Y. et al.: "Rap1 is involvcd in cell stretching modulation of p38 but not ERK or JNK MAP kinase"J. Cell Sci. 114. 1221-1227 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tobiume, K. et al.: "ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis"EMBO repotrs. 2. 222-228 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yanagisawa, M. et al.: "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7"Genes Cells. 6. 1091-1099 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsuzawa, A. et al.: "Physiological roles of ASK1-mediated signal transduction in oxidative stress-and endoplasmic reticulum stress-induced apoptosis : advanced findings from ASK1 knockout mice"Antioxidants and Redox Signal. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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