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Intracellular and extracellular metabolism of lipid mediators- DGK and LPA

Research Project

Project/Area Number 16590234
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionSapporo Medical University

Principal Investigator

KANOH Hideo  Sapporo Medical University School of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (70045475)

Co-Investigator(Kenkyū-buntansha) SAKANE Fumio  Sapporo Medical University School of Medicine, Department of Biochemistry, Associate Professor, 医学部, 助教授 (10183815)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsDiacylglycerol / Diacylglycerol kinase / Lipid phosphate phosphatase / Phosphatidic acid / Phosphatidic acid phosphatase / Signal transduction / ジアシルグリセロール キナーゼ / 脂質性メデイエーター / 細胞情報伝達 / リゾホスファチジン酸
Research Abstract

We investigated the function of two lipid-metabolizing enzymes, diacylglycerol kinase (DGK) and lipid phosphate phosphatase (LPP), expressed in various cells. DGK gamma was found to act as a suppressor of Rac-1, thus inhibiting lamellipodium formation in fibroblasts. This DGK isozyme was also translocated into the nuclei of various cells, resulting in an inhibition of cell growth. The PH domain of DGK delta was suggested to be involved in the plasma membrane translocation of this isozyme. The tenth member of DGK isozyme, DGK kappa, was cloned and its enzymatic properties were characterized. In the case of LPP, which acts at the outer cell surface, we found that the expression of LPP-1 or LPP-3 caused a marked suppression of the growth of various ovarian cancer cell lines, suggesting the importance of metabolizing extracellular lyso-phosphatidic acid in cancer cell proliferation.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (27 results)

All 2006 2005 2004 Other

All Journal Article (24 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Nuclear transportation of diacylpeol kinase gamma and its possible function in the nucleus2006

    • Author(s)
      Matsubara, M. et al.
    • Journal Title

      J. Biol. Chem. 281(10)

      Pages: 6152-6164

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nuclear transportation of diacylglycerol kinase gamma and its possible function in the nucleus.2006

    • Author(s)
      Matsubara, M. et al.
    • Journal Title

      J.Biol.Chem. 281(10)

      Pages: 6152-6164

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification and characterization of a novel human type II chiaphislyrolkinase, DGKκ.2005

    • Author(s)
      Imai, S. et al.
    • Journal Title

      J. Biol. Chem. 280(48)

      Pages: 39870-39881

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene expression, cellular localization and enzymatic activity of diacylglycerol kinase isozymes in rat ovary and placenta.2005

    • Author(s)
      Toya, M. et al.
    • Journal Title

      Cell Tissue Res. 320(3)

      Pages: 525-533

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression and localization of diacylglycerol kinase isozymes and enzymatic features in rat lung.2005

    • Author(s)
      Katagiri, Y. et al.
    • Journal Title

      Am.J.Physiol.Lung Cell Mol.Physiol. 288(16)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification and characterization of a novel human type II diacylglycerol kinase, DGK kappa.2005

    • Author(s)
      Imai, S. et al.
    • Journal Title

      J.Biol.Chem. 280(48)

      Pages: 39870-39881

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene expression, cellular localization and enzymatic activity of diacylglycerol kinase isozymes in rat ovary and placenta.2005

    • Author(s)
      Toya, M., Hozumi, Y., Ito, T.et al.
    • Journal Title

      Cell Tissue Res. 320

      Pages: 525-533

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression and localization of diacylglycerol kinase isozymes and enzymatic features in rat lung.2005

    • Author(s)
      Katagiri, Y., Ito, T.et al.
    • Journal Title

      Am.J.Physiol.Lung Cell Mol.Physiol. 288

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification and characterization of a novel human type II diacylglycerol kinase, DGKκ.2005

    • Author(s)
      Imai, S., Kai, M., Yasuda, S.et al.
    • Journal Title

      J.Biol.Chem. 280

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression and localization of diacylglycerol kinase isozymes and enzymatic features in rat lung2005

    • Author(s)
      Katagiri, Y.et al.
    • Journal Title

      Am.J.Physiol.Lung Cell Mol.Physiol. (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cloning and characterization of diacyldyent kuinasei splice variants is rat brain2004

    • Author(s)
      Ito, T.et al.
    • Journal Title

      J. Biol. Chem. 279(22)

      Pages: 23317-23326

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of immature protein by namics in the endoplasmic retiabem.2004

    • Author(s)
      Kamada, A. et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 21533-21542

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Diauphyarel kinase γserves as an upstream suppressor of Rac1 larmlbipocbiem formation2004

    • Author(s)
      Tsushima, S. et al.
    • Journal Title

      J. Biol. Chem. 279(27)

      Pages: 28603-28613

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heparein-beircleny EGF-like growth factor is a promisuy target for He therapy of ovarian cancer2004

    • Author(s)
      Miyamoto, S. et al.
    • Journal Title

      Cancer Res. 64(16)

      Pages: 5720-5727

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cloning and characterization of diacylglycerol kinase iota splice variants in rat brain2004

    • Author(s)
      Ito, T.et al.
    • Journal Title

      J.Biol.Chem. 279(22)

      Pages: 23317-23326

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Regulation of immature protein dynamics in the endoplasmic reticulum.2004

    • Author(s)
      Kamada, A. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 21533-21542

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Diacylglycerol kinase gamma serves as an upstream suppressor of Rac1 and lamellipodium formation.2004

    • Author(s)
      Tsushima S. et al.
    • Journal Title

      J.Biol.Chem. 279(27)

      Pages: 28603-28613

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The plasma membrane translocation of diacylglycerol kinase delta 1 is negatively regulated by conventional protein kinase C-dependent phosphorylation of Ser-22 and Ser-26 within the pleckstrin homology domain2004

    • Author(s)
      Imai, S. et al.
    • Journal Title

      Biochem.J. 382(Pt3)

      Pages: 957-966

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heparin-binding EGF-like growth factor is a promising target for the therapy of ovarian cancer.2004

    • Author(s)
      Miyamoto, S. et al.
    • Journal Title

      Cancer Res. 64(16)

      Pages: 5720-5727

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy2004

    • Author(s)
      Miyamoto, S.et al.
    • Journal Title

      Cancer Res 64(16)

      Pages: 5720-5727

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The plasma membrane translocation of diacylglycerol kinase delta1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain2004

    • Author(s)
      Imai, S.et al.
    • Journal Title

      Biochem.J. 382(3)

      Pages: 957-966

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Diacylglycerol kinase gamma serves as an upstream suppressor of Rac1 and lammellipodium formation2004

    • Author(s)
      Tsushima, S.et al.
    • Journal Title

      J.Biol.Chem. 279(27)

      Pages: 28603-28613

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of immature protein dynamics in the endoplasmic reticulum2004

    • Author(s)
      Kamada, A.et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 21533-21542

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nuclear transportation of diacylglycerol kinase gamma and its possible function in the nucleus

    • Author(s)
      Matsubara, M., Shirai, Y.et al.
    • Journal Title

      J.Biol.Chem. (In press)

    • Related Report
      2005 Annual Research Report
  • [Book] ジアシルグリヤロールキナーゼ(広川生物薬科学講座Vol.7)2005

    • Author(s)
      坂根郁夫, 山田恵子, 加納英雄
    • Publisher
      広川書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 広川生物薬科学講座 Vol.4(石橋、市川、堅田編)2005

    • Author(s)
      坂根郁夫, 山田恵子, 加納英雄
    • Publisher
      広川書店
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] DGKα阻害剤を有効成分として含有する抗癌剤2006

    • Inventor(s)
      坂根郁夫ほか4名
    • Industrial Property Rights Holder
      北海道
    • Industrial Property Number
      2006-095258
    • Filing Date
      2006-03-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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