Studies on the NFkB activation via diacylglycerol kinase alpha

• Project/Area Number: 20570135
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Sapporo Medical University
• Principal Investigator: KAI Masahiro Sapporo Medical University, 医学部, 講師 (80260777)
• Co-Investigator(Kenkyū-buntansha): SAKANE Fumio 札幌医科大学, 医学部, 准教授 (10183815)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: NFκB / アポトーシス / ジアシルグリセロールキナーゼ / メラノーマ / プロテインキナーゼC / 大腸がん / NFкB

Research Abstract

Using human melanoma cells, we demonstrated that diacylglycerol kinase (DGK) alpha enhanced tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear factor-kappaB (NF-kappaB) via protein kinase Czeta-dependent phosphorylation of a large subunit of NF-kappaB, p65/RelA. We found that the both of DGKalpha-specfic siRNA and TNF-alpha significantly attenuated the melanoma tumor growth in mice. DGKalpha is suggested to be a novel therapeutic target for melanoma.

Research Products

• [Journal Article] Diacylglycerol kinase α enhances protein kinase Cζ-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 Pages: 3265-3268
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase α enhances protein kinase Cζ-dependent phosphorylation at Ser311 of p65/RelA subunit of nuclear factor-κB (2009)
  • Author(s): Masahiro Kai
  • Journal Title: FEBS Lett 583 Pages: 3265-3268
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase η augments C-Raf activity and B-Raf/C-Rafheterodimerization (2009)
  • Author(s): Satoshi Yasuda
  • Journal Title: J Biol Chem 284 Pages: 29559-29570
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase δ associates with receptor for activated C kinase 1, RACK1. (2009)
  • Author(s): Shin-ichi Imai
  • Journal Title: Biochim Biophys Acta - Mol Cell Biol Lipid 1791 Pages: 246-253
  • 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 enhance the interaction of diacylglycerol kinase γ with the Src homology 2and C1 domains of β2-chimaerin. (2008)
  • Author(s): Satoshi Yasuda
  • Journal Title: Biochem. J. 409 Pages: 95-106
  • Peer Reviewed
• [Journal Article] Pulmonary surfactant protein D inhibits lipopolysacchaide (LPS)-induced inflammatory cell responses by altering LPS binding to its receptors. (2008)
  • Author(s): Yamazoe M.
  • Journal Title: J. Biol. Chem. 283 Pages: 35878-35888
  • Peer Reviewed
• [Journal Article] Pulmonary surfactant protein D binds MD-2 through the carbohydrate recognition domain. (2008)
  • Author(s): Nie, X
  • Journal Title: Biochemistry 47 Pages: 12878-12885
  • Peer Reviewed
• [Presentation] DGKG expression is epigenetically silenced in colorectal and gastric cancer cells (2010)
  • Author(s): 甲斐正広
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] 大腸がん・胃がん細胞におけるDGKγのエピジェネティック発現抑制 (2010)
  • Author(s): 甲斐正広
  • Organizer: 第33回日本分子生物学会年会 第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [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回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [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のシグナル伝達を仲介する (2009)
  • Author(s): 甲斐正広
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [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: In : 4th International Conference on Phospholipase A2 and Lipid Mediators
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2009-05-28
• [Presentation] Diacylglycerol kinase α suppresses tumor necrosis factor-α-induced apoptosis of human melanoma cells through NF-κB activation (2009)
  • Author(s): 甲斐正広
  • Organizer: 4th International Conference on Phospholipase A2 and Lipid Mediators
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2009-05-28
• [Presentation] Pulmonary collectins exhibit anti-microbial activity against Legionella pneumophila (2008)
  • Author(s): Sawada K.
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2008-12-12
• [Presentation] Pulmonary collectins interact with and aggregate Mycobacteriumavium (2008)
  • Author(s): Ariki S.
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2008-12-12
• [Presentation] Mutational analysis of Cys^<88>of Toll-Like receptor 4 highlights the critical role of MD-2 in cell surface receptor expression (2008)
  • Author(s): Nishitani C.
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2008-12-11
• [Presentation] 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依存性のNF-κB活性化にはプロテインキナーゼCζが関与する (2008)
  • Author(s): 甲斐正広、今井伸一、安田智、柳澤健二、豊田実、加納英雄、坂根郁夫
  • Organizer: 第31回日本分子生物学会年会/第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 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依存性のNF-/κ B活性化にはプロテインキナーゼC ζが関与する. (2008)
  • Author(s): 甲斐 正広
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 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依存性NF-κB活性化機構にはプロテインキナーゼCζが関与する (2008)
  • Author(s): 甲斐正広、今井伸一、安田智、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] 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依存性NF-κ B活性化機構にはプロテインキナーゼC ζが関与する. (2008)
  • Author(s): 甲斐 正広
  • 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] 肺コレクチンは非定型抗酸菌に結合し菌体凝集を惹起する (2008)
  • Author(s): 有木茂
  • Organizer: 第19回日本生体防御学会学術総会
  • Place of Presentation: 北海道大学学術交流会館
  • Year and Date: 2008-07-10
• [Presentation] レジオネラ菌に対する肺コレクチンの増殖抑制作用 (2008)
  • Author(s): 澤田格
  • Organizer: 第19回日本生体防御学会学術総会
  • Place of Presentation: 北海道大学学術交流会館
  • Year and Date: 2008-07-10
• [Presentation] TLR4の細胞表面発現におけるMD-2の重要性 (2008)
  • Author(s): 西谷千明
  • Organizer: 第19回日本生体防御学会学術総会
  • Place of Presentation: 北海道大学学術交流会館
  • Year and Date: 2008-07-10
• [Presentation] 肺サーフアクタント蛋白質Dによるリポ多糖惹起炎症反応の抑制 (2008)
  • Author(s): 山添雅己
  • Organizer: 第19回日本生体防御学会学術総会
  • Place of Presentation: 北海道大学学術交流会館
  • Year and Date: 2008-07-10