Analysis of DG kinase functions related to PKC and its application for future drug.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21570139
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kobe University
• Principal Investigator: SHIRAI Yasuhito 神戸大学, 大学院・農学研究科, 教授 (60263399)
• Project Period (FY): 2009 – 2011
• Keywords: 細胞情報伝達機構 / 脂質

Research Abstract

To elucidate function of DGK. in neurons, we developed DGK. KO mice using the Sleeping Beauty transposon system, and found that DGK. regulates spine formation by regulation of lipids, contributing to the maintenance of neural networks in synaptic transmission of cognitive processes including memory and emotion. Using DGK. KO mice, we investigated physiological role of DGK. in Vitamin E-induced improvement of diabetic renal dysfunction, and found that renal dysfunction of DGK. KO mice was sever and occurred earlier than WT. Finally, we discovered c-Src phosphorylated Tyr22 and Tyr334, while c-Abl phosphorylated 218Tyr.

Research Products

• [Journal Article] Regulation of diacylglycerol kinase by phosphorylation (2012)
  • Author(s): Shirai, Y., Ikeda, M., Saito, N.
  • Journal Title: Adv. biological. Reg. Volume: 52 Pages: 239-247
• [Journal Article] c-Abl tyrosine kinase regulates serum-induced nuclear export of diacylglycerol kinase・by phosphorylation at Tyr218 (2012)
  • Author(s): Matsubara, M., Ikeda, M., Kiso, Y., Sakuma, M., Sakane, F., Merida, I, Saito, N. and Shirai, Y.
  • Journal Title: J. Biol. Chem. Volume: 287 Pages: 5507-5517
• [Journal Article] Direct biding of RalA to PKC・and its crucial role in morphological change during keratinocytes differentiation (2011)
  • Author(s): Shirai, Y., Morioka, S., Sakuma, M., Yoshino, K., Otsuji, C., Sakai, N., Kashiwagi, K., Chida, K., Shirawaka, R., Horiuchi, H., Nishigori, C., Ueyama, T. and Saito, N
  • Journal Title: Mol. Biol. Cell Volume: 22 Pages: 1340-1352
• [Journal Article] Diacylglycerol kinase・・knockout mice exhibit lithium-sensitive behavioral abnormalities (2010)
  • Author(s): Kakefuda K., Oyagi A., Ishisaka, M., Tsumura, K., Shimazawa M., Yokota, K., Shirai Y., Horie K., Saito N., Takeda J. and Hara H.
  • Journal Title: PLoS ONE Volume: 5 Pages: e13447
• [Journal Article] Essential role of neuron-enriched diacylglycerol kinase(DGK), DGK・in neurite spine formation, contributing to cognitive function (2010)
  • Author(s): Shirai Y., Kouzuki T., Kakefuda K., Moriguchi S., Oyagi A., Horie K., Morita S., Shimazawa M., Fukunaga K., Takeda J., Saito N. and Hara H
  • Journal Title: PLoS ONE Volume: 5 Pages: e11602
• [Journal Article] Inflammatory cytokine TNF-alpha enhances NGF production in human keratinocytes, HaCaT cells (2009)
  • Author(s): Takaoka K., Shirai Y. and Saito N.
  • Journal Title: J. Pharmacol. Sci. Volume: 111 Pages: 381-391
• [Journal Article] An essential role of the aPKC-aurora A-NDEL1 pathway on neurite elongation by modulation of microtubule dynamics (2009)
  • Author(s): Mori D., Yamada M., Mimori-Kiyosue Y., Shirai Y., Suzuki A., Ohno S., Saya H., Wynshaw-Boris A. and Hirotsune H.
  • Journal Title: Nature Cell Biol Volume: 11 Pages: 1057-1068
• [Presentation] Physiological function of nuclear DGKαunder serum depleted conditions (2012)
  • Author(s): Y. Kiso, Y. Shirai, M. Sakuma, M. Ikeda, N. Saito
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] Function of PKC and DGK in neurons (2011)
  • Author(s): 白井康仁
  • Organizer: 2011 Taiwan-Japan Joint Symposium on Cell Signaling and Gene Regulation
  • Place of Presentation: 台湾・台南
  • Year and Date: 2011-11-19
• [Presentation] Regulation of diacylglycerolkinase by phosphorylation (2011)
  • Author(s): 白井康仁
  • Organizer: Fifty-Second International Symposium on "Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues"
  • Place of Presentation: イタリア・ボローニャ
  • Year and Date: 2011-09-26
• [Presentation] 異なるチロシンリン酸化によるジアシルグリセロールキナーゼalphaの局在調節機構 (2011)
  • Author(s): 白井康仁、池田もも、佐久間恵、木曽裕子、斎藤尚亮
  • Organizer: 第119回薬理学会近畿支部大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-07-08
• [Presentation] ジアシルグリセロールキナーゼ・の核移行と細胞周期制御に関する研究2-c-Ablによるチロシンリン酸化サイトの同定- (2011)
  • Author(s): 白井康仁、池田もも、木曽裕子、佐久間恵、齋藤尚亮
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-12
• [Presentation] Impairment of cognitive function and lithium-sensitive behavior of knockout mice of neuron-enriched subtype of DG kinase (2011)
  • Author(s): Y Shirai, T Kouzuki, K Kakefuda, A Ohyagi, K Horie, S Moriguchi, S Morita, M Shimazawa, K Fukunaga, J Takeda, N Saito, H Hara
  • Organizer: First annual meeting of International Society of Radiation Neurobiology
  • Place of Presentation: Maebashi, Japan
  • Year and Date: 2011-01-29
• [Presentation] Correlation between abnormal behavior and lipids contents of DGK・KO mice (2010)
  • Author(s): Y. Shirai
  • Organizer: The 5^<th> international mini-symposium on diacylglycerol kinase
  • Place of Presentation: DGK
  • Year and Date: 2010-12-11
• [Presentation] Nuclear diacylglycerol signaling regulated by nuclear-cytoplasmic shuttling of diacylglycerol kinase and its correlation to cell cycle control (2010)
  • Author(s): Y. Shirai and N. Saito
  • Organizer: BMB2010
  • Year and Date: 2010-12-08
• [Presentation] Membrane lipids control by neuron-enriched diacylglycerol kinase・is important for spine formation and cognitive function (2010)
  • Author(s): Y. Shirai, T. Kouzuki, K. Kakefuda, S. Moriguchi, A. Oyagi, K. Horie, S. Morita, M. Shimazawa, K. Fukunaga, J. Takeda, N. Saito and H. Hara
  • Organizer: Bioactive lipids : biochemistry and diseases
  • Year and Date: 2010-06-09
• [Presentation] Essential role of diacylglycerol kinase beta(DGKb) in neurite spine formation (2009)
  • Author(s): Y, Shirai
  • Organizer: Japan-Taiwan Joint Symposium on Cell Signaling and Gene Regulation
  • Year and Date: 2009-11-12
• [Presentation] Essential role of diacylglycerol kinase beta(DGK・・in neurite spine formation, cognitive function and memory (2009)
  • Author(s): Y, Shirai
  • Organizer: Neuroscience 2009
  • Year and Date: 2009-10-22
• [Presentation] Important role of diacylglycerol kinase・in spine formation and memory (2009)
  • Author(s): 白井康仁
  • Organizer: 日本神経科学大会
  • Year and Date: 2009-09-18
• [Presentation] ジアシルグリセロールキナーゼ・ノックアウトマウスはスパイン形成異常と記憶障害を示す-スパイン形成における脂質シグナリングの重要性- (2009)
  • Author(s): 白井康仁
  • Organizer: 脂質生化学会
  • Year and Date: 2009-07-30
• [Remarks]
  • URL: http://www2.kobe-u.ac.jp/~shirai/
• [Patent(Industrial Property Rights)] DGKγをターゲットとする抗アレルギー剤のスクリーニング方法 (2011)
  • Inventor(s): 白井康仁、斎藤尚亮
  • Industrial Property Rights Holder: 神戸大学
  • Industrial Property Number: 特許、2011-1415
  • Filing Date: 2011-06-27