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

• Project/Area Number: 21770147
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: National 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: ¥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.

Research Products

• [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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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