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

• 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
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 細胞情報伝達機構 / 脂質 / ジアシルグリセロールキナーゼ / プロテインキナーゼC / 脂質シグナル / 神経 / 糖尿病 / スパイン / LTP / 腎症 / 脂質キナーゼ / ジアシルグリセロール / フォスファチジン酸 / 記憶 / KOマウス

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] c-Abl tyrosine kinase regulates serum-induced nuclear export of diacylglycerol kinase α by phosphorylation at Tyr218 (2011)
  • Author(s): Matsubara, M., Ikeda, M., Kiso, Y., Sakuma, M., Sakane, F., Merida, I, Saito, N., Shirai, Y.
  • Journal Title: J.Biol.Chem Volume: 287 Issue: 8 Pages: 5507-5517
  • DOI: 10.1074/jbc.m111.296897
  • Peer Reviewed
• [Journal Article] Regulation of diacylglycerol kinase by phosphorylation (2011)
  • Author(s): Shirai, Y., Ikeda, M., Saito, N.
  • Journal Title: Adv.Enz.Reg. Volume: (Web) Issue: 1 Pages: 239-247
  • DOI: 10.1016/j.advenzreg.2011.09.004
  • Peer Reviewed
• [Journal Article] Streptococcus mutans diacylglycerol kinase homologue : a potential target for anti-caries chemotherapy (2011)
  • Author(s): Shibata, Y., Kawada-matsuo, M., Shirai, Y., Saito, N., Li, D., Yamashita, Y.
  • Journal Title: J.Medical Microbiol. Volume: 60 Pages: 625-630
  • NAID: 120004951599
  • Peer Reviewed
• [Journal Article] Direct biding of RalA to PKCη 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., Saito, N.
  • Journal Title: Mol.Biol.Cell Volume: 22 Pages: 1340-1352
  • Peer Reviewed
• [Journal Article] A critical role of conventional protein kinase C in morphological changes of rodent mast cells. (2011)
  • Author(s): Yanase Y., Hide I, Mihara S., Shirai Y., Saito N., Nakata Y., Hide M., Sakai N.
  • Journal Title: Immunol.Cell.Biol Volume: 83 Pages: 149-159
  • Peer Reviewed
• [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
• [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
• [Journal Article] DGKβ 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., Hara H.
  • Journal Title: PLoS ONE Volume: 5
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase β 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., Hara H.
  • Journal Title: PLoS ONE Volume: 5
  • Peer Reviewed
• [Journal Article] Suppression mechanisms of flavaonoids on aryl hydrocarbon receptor-mediated signal transduction. (2010)
  • Author(s): Mukai R, Shirai Y., Saito N., Fukuda I., Nishiumi S., Yoshida K., Ashida H.
  • Journal Title: Arch.Biochem.Biophys Volume: 501 Pages: 134-141
  • Peer Reviewed
• [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
• [Journal Article] Kinase activity of the dgk gene product is involved in the virulence of Streptococcus mutants. (2009)
  • Author(s): Shibata Y., van der Ploeg JR., Kozuki T., Shirai Y, Saito N, Kawada-Matsuo M, Takeshita T, Yamashita Y
  • Journal Title: Microbiology 155 Pages: 557-565
  • Peer Reviewed
• [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., Hirotsune H
  • Journal Title: Nature Cell Biol. 11 Pages: 1057-1068
  • Peer Reviewed
• [Journal Article] Inflammatory cytokine TNF-alpha enhances NGF production in human keratinocytes, HaCaT cells (2009)
  • Author(s): Takaoka K., Shirai Y., Saito N
  • Journal Title: J.Pharmacol.Sci. 111 Pages: 381-391
  • Peer Reviewed
• [Presentation] 筋肉細胞におけるEGCgの糖代謝に及ぼす影響について (2012)
  • Author(s): 上田学、上田修司、白井康仁、芦田均
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都女子大学(京都府)
  • Year and Date: 2012-03-23
• [Presentation] ジアシルグリセロールキナーゼθの機能解析 (2012)
  • Author(s): 上田修司、桐村悠佑、山之上稔、白井康仁
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都女子大学(京都府)
  • Year and Date: 2012-03-23
• [Presentation] PKCηによるケラチノサイト分化機構の解明 (2012)
  • Author(s): 白井康仁、盛岡祥子、佐久間恵、千田和広、斎藤尚亮
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都女子大学(京都府)
  • Year and Date: 2012-03-23
• [Presentation] The role of diacylglycerol kinase in the degranulation from RBL-2H3 mast cells (2012)
  • Author(s): M.Sakuma, Y.Shirai, T.Ueyama, N.Saito
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2012-03-16
• [Presentation] Diacylglycerol kinase as a possible drug target (2012)
  • Author(s): Y.Shirai, N.Saito
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2012-03-15
• [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] Physiological function of nuclear DGKα under 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: 国立京都国際会館(京都府)
  • 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] 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: 台南(台湾)
  • 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] Regulation of diacylglycerolkinase by phosphorylation (2011)
  • Author(s): Y.Shirai, N.Saito
  • Organizer: Fifty-Second International Symposium on "Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues"
  • Place of Presentation: ボローニャ(イタリア)
  • Year and Date: 2011-09-26
• [Presentation] ジアシルグリセロールキナーゼβ(DGKβ)による神経特異的突起伸長機構の解明 (2011)
  • Author(s): 中井寛子、加野拓也、上月健、斉藤尚亮、中嶋昭雄、吉川潮、上田修司、山之上稔、白井康仁
  • Organizer: 第3回神戸大学バイオサイエンス研究会・若手研究者交流会
  • Place of Presentation: 神戸大学(兵庫県)
  • Year and Date: 2011-09-06
• [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] 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: ウィンクあいち(愛知県)
  • 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] ジアシルグリセロールキナーゼα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: ホテル東京ガーデンパレス(東京都)
  • 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] Correlation between abnormal behavior and lipids contents of DGKβ KO mice (2010)
  • Author(s): Y.Shirai, N.Saito
  • Organizer: The 5^<th> international mini-symposium on diacylglycerol kinase (DGK).
  • Place of Presentation: 神戸本学(兵庫県)
  • 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] Nuclear diacylglycerol signaling regulated by nuclear-cytoplas mic shuttling of diacylglycerol kinase α and its correlation to cell cycle control (2010)
  • Author(s): Y.Shirai, N.Saito
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートヲイランド(兵庫県)
  • Year and Date: 2010-12-08
• [Presentation] Visualization of protein kinase C and diacylglycerol kinase in living cells (2010)
  • Author(s): Y.Shirai, N.Saito
  • Organizer: 28^<th> JES summer seminar on Endocrinology & Metabolism.
  • Place of Presentation: 長崎大学(長崎県)(招待講演)
  • Year and Date: 2010-07-08
• [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] Membrane lipids control by neuron-enriched diacylglycerol kinaseβ 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, H.Hara
  • Organizer: Keystone symposia "Bioactive lipids : biochemistry and diseases
  • Place of Presentation: ウェスティン都京都(京都府)(招待講演)
  • 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(DGKβ)in neurite spine for mation, coginitive function and memory (2009)
  • Author(s): 白井康仁
  • Organizer: Japan-Taiwan Joint Symposium on Cell Signaling and Gene Regulation
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • 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] Essential role of diacylglycerol kinase beta(DGKβ)in neurite spine formation, cognitive function and memory (2009)
  • Author(s): 白井康仁
  • Organizer: Neuroscience 2009
  • Place of Presentation: McCormick Place Convention Center(Chicago, USA)
  • 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] Important role of diacylglycerol kinase β in spine formation and memory (2009)
  • Author(s): 白井康仁
  • Organizer: 日本神経科学大会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • 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
• [Presentation] ジアシルグリセロールキナーゼβ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
  • Place of Presentation: ウイル愛知(愛知県)
  • Year and Date: 2009-07-30
• [Book] 基礎生物学テキストシリーズ2 分子生物学 (2011)
  • Author(s): 深見泰夫編
  • Total Pages: 237
  • Publisher: 化学同人
• [Remarks]
  • URL: http://www2.kobe-u.ac.jp/~shirai/
• [Remarks]
  • URL: http://www2.kobe-u.ac.jp/~shirai/
• [Remarks]
  • URL: http://www2.kobe-u.ac.jp/~shirai/
• [Remarks]
  • URL: http://www.research.kobe-u.ac.jp/brce-saito/publications.html
• [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
  • Filing Date: 2011-06-27
• [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
  • Filing Date: 2011-06-27