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Elucidation of the mechanism by which diacylglycerol kinase η regulates cell proliferation

Research Project

Project/Area Number 21770147
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Functional biochemistry
Research InstitutionNational Institute of Health Sciences

Principal Investigator

YASUDA Satoshi  National Institute of Health Sciences, 遺伝子細胞医薬部, 主任研究官 (20381262)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsシグナル伝達 / 脂質 / 酵素
Research Abstract

The Ras/B-Raf/C-Raf/MEK/ERK pathway (ERK pathway) is critical for the control of many cellular processes including proliferation. Here we showed that siRNA-dependent knockdown of diacylglycerol kinase η (DGK η) impairs the ERK pathway activated by epidermal growth factor (EGF) in HeLa cells. The overexpression of DGK η could activate the ERK pathway in a DGK activity-independent manner, suggesting that DGK η serves as an adaptor protein. We revealed that DGK η activates C-Raf but not B-Raf. Moreover, knockdown of DGK η inhibited EGF-induced heterodimerization of C-Raf with B-Raf. DGK η physically interacted with B-Raf and C-Raf and regulated EGF-induced recruitment of B-Raf and C-Raf from the cytosol to membranes. These results support that DGK η acts as a novel critical regulatory component of the ERK signaling cascade.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (12 results)

All 2011 2009

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (8 results)

  • [Journal Article] Diacylglycerol kinase η augments C-Raf activity and B-Raf/C-Raf heterodimerization.2009

    • Author(s)
      Yasuda, S, Kai, M, Imai,S, Takeishi, K, Taketomi, A, Toyota, M, Kanoh, H, Sakane, F
    • Journal Title

      J.Biol. Chem. 284(43)

      Pages: 29559-29570

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diacylglycerol kinase α enhances protein kinase C ζ-dependent phosphorylation at Ser311 of p65/RelA subunit of nuclear factor-κB.2009

    • Author(s)
      Kai, M, Yasuda, S, Imai, S, Toyota, M, Kanoh, H, Sakane, F
    • Journal Title

      FEBS Lett. 583(19)

      Pages: 3265-3268

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf heterodimerization.2009

    • Author(s)
      Satoshi Yasuda
    • Journal Title

      J.Biol.Chem. 284

      Pages: 29559-29570

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diacylglycerol kinase alpha enhances protein kinase Czeta-dependent phosphorylation at Ser311 of p65/RelA subunit of nuclear factor-kappaB.2009

    • Author(s)
      Masahiro Kai
    • Journal Title

      FEBS Lett. 583

      Pages: 3265-3268

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] マウス胚性癌細胞および胚性幹細胞における心筋分化能マーカーの検索2011

    • Author(s)
      安田智
    • Organizer
      第10回 日本再生医療学会
    • Place of Presentation
      東京
    • Year and Date
      2011-03-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] マウス胚性癌細胞および胚性幹細胞における心筋分化能マーカーの検索2011

    • Author(s)
      安田智、長谷川哲也、細野哲司、佐藤光利、山口照英、鈴木和博、佐藤陽治
    • Organizer
      第10回日本再生医療学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] ジアシルグリセロールキナーゼηは上皮増殖因子に依存したRafシグナル経路を制御する2009

    • Author(s)
      安田智
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] ジアシルグリセロールキナーゼηは、上皮増殖因子に応答してB-RAFとC-RAFの相互作用を促進し、MEK-ERK経路を活性化する2009

    • Author(s)
      安田智
    • Organizer
      第51回日本脂質生化学会
    • Place of Presentation
      ウィルあいち(名古屋市)
    • Year and Date
      2009-07-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] ジアシルグリセロールキナーゼηは上皮増殖因子に依存したRAFシグナル経路を制御する2009

    • Author(s)
      安田智、今井伸一、甲斐正広、鈴木拓、今井浩三、豊田実、坂根郁夫
    • Organizer
      第68回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] PKCζによるp65のリン酸化がメラノーマ細胞におけるジアシルグリセロールキナーゼαからNF-κBへのシグナル伝達を仲介する2009

    • Author(s)
      甲斐正広、安田智、今井伸一、鈴木拓、今井浩三、豊田実、坂根郁夫
    • Organizer
      第68回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] ジアシルグリセロールキナーゼηは、上皮増殖因子に応答してB-RAFとC-Rafの相互作用を促進し、MEK-ERK経路を活性化する2009

    • Author(s)
      安田智、坂根郁夫
    • Organizer
      第51回日本脂質生化学会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Final Research Report
  • [Presentation] Diacylglycerol kinase α suppresses tumor necrosis factor-α-induced apoptosis of human melanoma cells through NF-κB activation.2009

    • Author(s)
      Kai, M, Yanagisawa, K, Yasuda, S, Sakane, F.
    • Organizer
      4th International Conference on Phospholipase A_2 and Lipid Mediators
    • Place of Presentation
      Tokyo
    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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