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Investigation of the regulation mechanism of tumor necrosis factor α converting enzyme by type II diacylglycerol kinases

Research Project

Project/Area Number 16570119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionSapporo Medical University

Principal Investigator

IMAI Shin-ichi  Sapporo Medical University, School of Medicine, Instructor, 医学部, 助手 (20213209)

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: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsdiacylglyicerol kinase / diacylglyicerol / phosphatidic acid / isozyme / PH domain / tyrosine phosphorylation / oxidative stress
Research Abstract

Diacylglycerol kinase (DGK) plays an important role in signal transduction through modulating the balance between two signaling lipids, diacylglycerol and phosphatidic acid. We identified a tenth member of the DGK family designated DGKκ. The κ-isozyme (1271 amino acids, calculated molecular mass = 142 kDa) contains a pleckstrin homology domain, two cysteine-rich zinc finger-like structures and a separated catalytic region as have been found commonly in the type II isozymes previously cloned (DGKδ and DGKη). The new DGK isozyme has additionally 33 tandem repeats of Glu-Pro-Ala-Pro at the N terminus. Reverse transcriptase-PCR showed that the DGKκ mRNA is most abundant in the testis, and to a lesser extent in the placenta. DGKκ, when expressed in HEK293 cells, was persistently localized at the plasma membrane even in the absence of cell stimuli. Deletion analysis revealed that the short C-terminal sequence (amino acid residues 1199-1268) is necessary and sufficient for the plasma membrane localization. Interestingly, DGKκ, but not other type II DGKs, was specifically tyrosine-phosphorylated at Tyr-78 through the Src family kinase pathway and in H_2O_2-treated cells. Moreover, H_2O_2 selectively inhibited DGKκ activity in a Src family kinase-independent manner, suggesting that the isozyme changes the balance of signaling lipids in the plasma membrane in response to oxidative stress. The expression patterns, subcellular distribution, and regulatory mechanisms of DGKκ are distinct from those of DGKδ and DGKη despite high structural similarity, suggesting unique functions of the individual type II isozymes.

Report

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

    (8 results)

All 2005 2004

All Journal Article (8 results)

  • [Journal Article] Identification and characterization of a novel human type II diacylglycerol kinase, DGKκ2005

    • Author(s)
      Shin-ichi Imai
    • 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] Identification and characterization of a novel human type II diacylglycerol kinase, DGKκ2005

    • Author(s)
      Shin-ichi Imai
    • 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] Identification and characterization of a novel human type II diacylglycerol kinase, DGKκ2005

    • Author(s)
      Shin-ichi Imai
    • Journal Title

      J.Biol.Chem. 280・48

      Pages: 39870-39881

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The plasma membrane translocation of diacylglycerol kinase δ1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-26 within the pleckstrin homology domain2004

    • Author(s)
      Shin-ichi Imai
    • Journal Title

      Biochem. J. 382・Pt3

      Pages: 957-966

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Diacyglycerol kinase γ serves as an upstream suppressor of Racl and lamellipodium formation2004

    • Author(s)
      Shuichi Tushima
    • 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] The plasma membrane translocation of diacylglycerol kinase δ1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain2004

    • Author(s)
      Shin-ichi Imai
    • Journal Title

      Biochem.J. 382(Pt.3)

      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] Diacylglycerol kinase γ serves as an upstream suppressor of Rac 1 and lamellipodium formation2004

    • Author(s)
      Shuichi Tsushima
    • 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 delta1 is negatively regulated by conventional protin kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain2004

    • Author(s)
      Shin-ichi Imai
    • Journal Title

      Biochem.J. 382・3

      Pages: 957-966

    • Related Report
      2004 Annual Research Report

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

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