Elucidation of the mechanism by which diacylglycerol kinase γ regulates cytoskeleton reorganization

• Project/Area Number: 19790065
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Sapporo Medical University
• Principal Investigator: YASUDA Satoshi Sapporo Medical University, 医学部, 助教 (20381262)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 脂質 / 細胞内情報伝達 / 酵素

Research Abstract

細胞骨格系の制御は細胞の伸展や遊走に深く関わっている。Rhoファミリー低分子量Gタンパク質であるRacの活性化は、細胞骨格の構成分子であるアクチンの再構築を促し、葉状仮足形成を引き起こす。脂質代謝酵素ジアシルグリセロールキナーゼγ(DGKγ)は、Racを不活性化し葉状仮足形成を抑制するが、そのメカニズムは不明であった。本研究によって、Racを不活性化するβ2-chimaerinをDGKγが活性化する機構が明らかとなった。

Research Products

• [Journal Article] Diacylglycerol kinase δ associates with receptor for activated C kinase 1, RACK1. (2009)
  • Author(s): Imai S, Yasuda S, Kai M, Kanoh H, Sakane F
  • Journal Title: Biochim. Biophys. Acta-Mol. Cell Biol. Lipids 1791 Pages: 246-253
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase σ associates with receptor for activated C kinase 1, RACK1 (2009)
  • Author(s): Shin-ichi Imai
  • Journal Title: Biochim. Biophys. Acta-Mol. Cell Biol. Lipids 1791 Pages: 246-253
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinases as emerging potential drug targets for a variety of diseases (2008)
  • Author(s): Sakane F., Imai S., Kai M., Yasuda S., Kanoh H.
  • Journal Title: Curr. Drug Targets 9 Pages: 626-640
  • Peer Reviewed
• [Journal Article] Phorbol ester and hydrogen peroxide synergistically induce the interaction of diacylglycerol kinase γ with the Src homology 2 and C1 domains of β2-chimaerin (2008)
  • Author(s): Yasuda S, Kai M, Imai S, Kanoh H, Sakane F
  • Journal Title: Biochem. J 409 Pages: 95-106
  • Peer Reviewed
• [Journal Article] Rab7 regulates maturation of the melanosomal matrix protein gp100/Pmel17/Silv (2008)
  • Author(s): Kawakami A, Sakane F, Imai S, Yasuda S, Kai M, Kanoh H, Jin H-Y, Hirosaki K, Yamashita T, Fisher DE, Jimbow K
  • Journal Title: J. Invest. Dermatol 128 Pages: 143-150
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinases as emerging potential drug targets for a variety of diseases (2008)
  • Author(s): Fumio Sakane
  • Journal Title: Curr. Drug Targets 9 Pages: 626-640
  • Peer Reviewed
• [Journal Article] Phorbol ester and hydrogen peroxide synergistically induce the interaction of diacylglycerol kinase γ with the Src homology 2 and C1 domains of β2-chimaerin (2008)
  • Author(s): Satoshi Yasuda
  • Journal Title: Biocherm.J. 409 Pages: 95-106
  • Peer Reviewed
• [Journal Article] Rab7 regulates maturation of the melanosomal matrix proteingp 100/Pmel17/Silv (2008)
  • Author(s): Akinori Kawakami
  • Journal Title: J.Invest.Dermatol 128 Pages: 143-150
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase α suppresses tumor necrosis factor-α-induced apoptpsis of human melanoma cells through NF-κB axtivation (2008)
  • Author(s): Kenji Yanagisawa
  • Journal Title: Biochim.Biophys.Acta-Mol.Cell Biol.Lipids 1771 Pages: 462-474
  • Peer Reviewed
• [Journal Article] Tyrosine phosphorylation of β2-chimaerin by Src-family kinase negatively regulates its Rac-specific GAP activity (2007)
  • Author(s): Kai M, Yasuda S, Imai S, Kanoh H, Sakane F
  • Journal Title: Biochim. Biophys. Acta-Mol. Cell Res 1773 Pages: 1407-1415
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinases: Why so many of them? (2007)
  • Author(s): Sakane F., Imai S., Kai M., Yasuda S., Kanoh H.
  • Journal Title: Biochim. Biophys. Acta-Mol. Cell Biol. Lipids 1771 Pages: 793-806
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase a suppresses tumor necrosis factor-α-induced apoptosis of human melanoma cells through NF-kB activation (2007)
  • Author(s): Yanagisawa K, Yasuda S, Kai M, Imaik S, Yamada K, Yamashita T, Jimbow K, Kanoh H, Sakane F
  • Journal Title: Biochim. Biophys. Acta-Mol. Cell Biol. Lipids 1771 Pages: 462-474
  • Peer Reviewed
• [Journal Article] Tyrosine phosphorylation of β2-chimaerin by Src-family kinase negatively regulates its Rac-specific GAP activity (2007)
  • Author(s): Masahiro Kai
  • Journal Title: Biochim.Biophys.Acta-Mol.Cell Res. 1773 Pages: 1407-1415
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinases:Why so many of them (2007)
  • Author(s): Fumio Sakane
  • Journal Title: Biochim.Biophys.Acta-Mol.Cell Biol.Lipids 1771 Pages: 793-806
  • Peer Reviewed
• [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C-RAFを活性化し、細胞増殖を促進する (2008)
  • Author(s): 安田智、今井伸一、甲斐正広、豊田実、坂根郁夫
  • Organizer: BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [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C-RAFを活性化し、細胞増殖を促進する。 (2008)
  • Author(s): 安田智
  • Organizer: BMB2008
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [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たRAF-MEK-ERK経路を活性化し、細胞増殖を促進する (2008)
  • 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67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [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たRAF-MEK-ERK経路を活性化し、細胞増殖を促進する。 (2008)
  • Author(s): 安田智
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] 細胞刺激に応答したジアシルグリセロールキナーゼγによるβ2-chimaerin活性化機構 (2007)
  • Author(s): 安田智、甲斐正広、今井伸一、坂根郁夫、加納英雄
  • Organizer: BMB2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] ジアシルグリセロールキナーゼγは細胞刺激に応答しβ2-chimaerin(Rac特異的GAP)を活性化する (2007)
  • Author(s): 安田智、甲斐正広、今井伸一、坂根郁夫、加納英雄
  • Organizer: 日本脂質生化学会
  • Place of Presentation: 日本脂質生化学会
  • Year and Date: 2007-06-06
• [Presentation] ジアシルグリセロールキナーゼγは細胞刺激に応答しβ2-chimaerin(Rac特異的GAP)を活性化する (2007)
  • Author(s): 安田 智
  • Organizer: 日本脂質生化学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-06-06