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Analysis of stress-activated signal transduction pathway by using nematode as a model animal.

Research Project

Project/Area Number 14086206
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNagoya University

Principal Investigator

HISAMOTO Naoki  Nagoya University, Graduate School of Science Department of Biological Science, Associate Professor (80283456)

Project Period (FY) 2002 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥81,000,000 (Direct Cost: ¥81,000,000)
Fiscal Year 2006: ¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2005: ¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2004: ¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2003: ¥15,600,000 (Direct Cost: ¥15,600,000)
Fiscal Year 2002: ¥15,600,000 (Direct Cost: ¥15,600,000)
KeywordsJNK / p38 / C.elegans / MAPキナーゼ / ストレス応答 / シグナル伝達 / C.elegans / ストレス
Research Abstract

We determined the relationship between stresses by infection and MAPK cascades in nematode. As a result, we showed that a p38 MAPK cascade, consisting of NSY-1, SEK-1 and PMK-1, has an important role in innate immunity against infectious bacteria, such as Pseudomonas. We also found that VHP-1, a MAPK phosphatase, negatively regulates this cascade.
Relationships between oxidative stresses and MAPK cascades in nematodes were determined. As a result, we found that a MAPK cascade, consisting of SEK-1 and PMK-1, is activated in intestine by the oxidative stresses. In addition, we showed that the activated SEK-1-PMK-1 MAPK cascade confers resistance of oxidative stress in whole organism by inducing transcription of GCS-1, a nematode homolog of glutathione synthesis enzyme, via a transcription factor SKN-1.
We determined the relationship between responses against heavy metal stresses and MAPK cascades in nematode. As a result, we found that a JNK MAPK cascade, consisting of MLK-1, MEK-1 and KGB-1, is required for resistance against heavy metal stresses, and VHP-1 functions as a negative regulator of this cascade. In addition, we genetically showed that a p38 MAPK cascade, consisting of SEK-1 and PMK-1, weakly contributes to the resistance and is negatively regulated by VHP-1.
We showed that UNC-16, a nematode homolog of JIP3 and a scaffold protein of JNK, associates with kinesin and regulates localization of synaptic vesicles by transporting UNC-14, an autophagy regulator protein, to the appropriate positions.

Report

(6 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (33 results)

All 2007 2005 2004 2002 Other

All Journal Article (30 results) Publications (3 results)

  • [Journal Article] LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins.2007

    • Author(s)
      Sakaguchi-Nakashima, Aisa
    • Journal Title

      Current Biology 17

      Pages: 592-598

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins.2007

    • Author(s)
      Sakaguchi-Nakashima, A., Meir, J. Y., Jin, Y., ^*Matsumoto, K., Hisamoto, N.
    • Journal Title

      Curr. Biol. 17

      Pages: 592-598

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins2007

    • Author(s)
      Sakaguchi-Nakashima et al.
    • Journal Title

      Current Biology 17

      Pages: 592-598

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1・ in oxidative stress response.2005

    • Author(s)
      Inoue, Hideki
    • Journal Title

      Genes and Development 19

      Pages: 2278-2283

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regulation of the Caenorhabditis elegans oxidative stress defence protein SKN-1 by glycogen synthase kinase-3.2005

    • Author(s)
      An, Jae Hyung
    • Journal Title

      Proceedings of the National Academy of Sciences of the USA 102

      Pages: 16275-16280

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Caenorhabditis elegans UNC-14 RUN domain protein binds to the Kinesin-1 and UNC-16 complex and regulates synaptic vesicle localization.2005

    • Author(s)
      Sakamoto, Rie
    • Journal Title

      Molecular Biology of the Cell 16

      Pages: 483-496

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1.2005

    • Author(s)
      Moriguchi, Tetsuo
    • Journal Title

      The Journal of Biological Chemistry 280

      Pages: 42685-42693

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response.2005

    • Author(s)
      Inoue, H., Hisamoto, N., An, J. H., Oliveira, R. P., Nishida, E., Blackwell, T. K., ^*Matsumoto, K.
    • Journal Title

      Genes Dev. 19

      Pages: 2278-2283

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regulation of the Caenorhabditis elegans oxidative stress defence protein SKN-1 by glycogen synthase kinase-3.2005

    • Author(s)
      An, J. H., Vranas, K., Lucke, M., Inoue, H., Hisamoto, N., Matsumoto, K., ^*Blackwell, T. K.
    • Journal Title

      Proc. Natl. Acad. Sci. U S A. 102

      Pages: 16275-16280

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Caenorhabditis elegans UNC-14 RUN domain protein binds to the Kinesin-1/UNC-16 complex and regulates synaptic vesicle localization.2005

    • Author(s)
      Sakamoto, R., Byrd, D. T., Hisamoto, N., ^*Matsumoto, K., ^*Jin, Y.
    • Journal Title

      Mol. Biol. Cell 16

      Pages: 483-496

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1.2005

    • Author(s)
      Moriguchi, T., Urushiyama, S., Hisamoto N., Iemura, S., Uchida, S., Natsume, T., Matsumoto, K., ^*Shibuya H.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 42685-42693

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The C.elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response.2005

    • Author(s)
      Inoue et al.
    • Journal Title

      Genes and Development 19(19)

      Pages: 2278-2283

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of the Caenorhabditis elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-32005

    • Author(s)
      An et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 102(45)

      Pages: 16275-16280

    • Related Report
      2005 Annual Research Report
  • [Journal Article] WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1.2005

    • Author(s)
      Moriguchi et al.
    • Journal Title

      J. Biol. Chem. 280(52)

      Pages: 42685-42693

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The Caenorhabditis elegans UNC-14 RUN domain protein binds to the kinesin-1 and UNC-16 complex and regulates synaptic vesicle localization.2005

    • Author(s)
      Sakamoto et al.
    • Journal Title

      Molecular Biology of the Cell 16(2)

      Pages: 483-496

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase.2004

    • Author(s)
      Kim, Dennis H.
    • Journal Title

      Proceedings of the National Academy of Sciences of the USA 101

      Pages: 10990-10994

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Caenorhabditis elegans MAPK phosphatase VHP-1 mediates a novel JNK-1ike signaling pathway in stress response.2004

    • Author(s)
      Mizuno, Tomoaki
    • Journal Title

      The EMBO Journal 23

      Pages: 2226-2234

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] An NDPase links ADAM protease glycosylation with organ morphogenesis in C. elegans.2004

    • Author(s)
      Nishiwaki, Kiyoji
    • Journal Title

      Nature Cell Biology 6

      Pages: 31-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Roles of MAP kinase cascades in Caenorhabditis elegans.2004

    • Author(s)
      Sakaguchi, Aisa
    • Journal Title

      Journal of Biochemistry 136

      Pages: 7-11

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The C. elegans UNC-14 RUN domain protein binds to the Kinesin-1/UNC-16 complex and regulates synaptic vesicle localization.2004

    • Author(s)
      Sakamoto, Rie
    • Journal Title

      Molecular Biology of the Cell 16

      Pages: 483-496

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase.2004

    • Author(s)
      Kim, D. H., Liberati, N. T., Mizuno, T., Hisamoto, N., Matsumoto, K., ^*Ausubel, F. M
    • Journal Title

      Proc. Natl. Acad. Sci. USA. 101

      Pages: 10990-10994

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Caenorhabditis elegans MAPK phosphatase VHP-1 mediates a novel JNK-like signaling pathway in stress response.2004

    • Author(s)
      Mizuno, T., Hisamoto, N., Terada, T., Kondo, T., Adachi, M., Nishida, E., Kim, D. H., Ausubel, F. M., ^*Matsumoto, K.
    • Journal Title

      EMBO J. 23

      Pages: 2226-2234

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] An NDPase links ADAM protease glycosylation with organ morphogenesis in C. elegans.2004

    • Author(s)
      ^*Nishiwaki, K., Kubota, Y., Chigira, Y., Roy, S. K., Suzuki, M., Schvarzstein, M., Jigami, Y., Hisamoto, N., Matsumoto, K.
    • Journal Title

      Nat. Cell Biol. 6

      Pages: 31-37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Roles of MAP kinase cascades in Caenorhabditis elegans.2004

    • Author(s)
      Sakaguchi, A., Matsumoto, K., Hisamoto, N.
    • Journal Title

      J. Biochem. (Tokyo) 136

      Pages: 7-11

    • NAID

      10016200538

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The C. elegans UNC-14 RUN domain protein binds to the Kinesin-1/UNC-16 complex and regulates synaptic vesicle localization.2004

    • Author(s)
      Sakamoto, R., Byrd, D. T., Hisamoto, N., Matsumoto, K., ^*Jin, Y.
    • Journal Title

      Mol. Biol. Cell 16

      Pages: 483-496

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Roles of MAP kinase cascades in Caenorhabditis elegans.2004

    • Author(s)
      Sakaguchi et al.
    • Journal Title

      Journal of Biochemistry 136(1)

      Pages: 7-11

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase.2004

    • Author(s)
      Kim et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101(30)

      Pages: 10990-10994

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The Caenorhabditis elegans MAPK phosphatase VHP-1 mediates a novel JNK-like signaling pathway in stress response.2004

    • Author(s)
      Mizuno et al.
    • Journal Title

      EMBO J. 23(11)

      Pages: 2226-2234

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity.2002

    • Author(s)
      Kim, Dennis H.
    • Journal Title

      Science 297

      Pages: 623-626

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity.2002

    • Author(s)
      Kim, D. H., Feinbaum, R., Alloing, G., Emerson, F. E., Garsin, D. A., Inoue, H., Tanaka-Hino, M., Hisamoto, N., Matsumoto, K., Tan, M. W., ^*Ausubel, F. M.
    • Journal Title

      Science 297

      Pages: 623-626

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Publications] Nishiwaki, K.: "An NDPase links ADAM protease glycosylation with organ morphogenesis in C. elegans"Nature cell Biology. 6. 31-37 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kim, DH.: "A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity"Science. 297(5581). 623-626 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka-Hino, M: "SEK-1 MAPKK mediates Ca^<2+> signaling to determine neuronal asymmetric development in Caenorhabditis elegans"ENBO Reports. 3(1). 56-62 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2018-03-28  

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