Comprehensive investigation of molecular mechansim of intracellular localization of DG kinase as an example of general enzmes

• Project/Area Number: 15K07002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kobe University
• Principal Investigator: Shirai Yasuhito 神戸大学, 農学研究科, 教授 (60263399)
• Co-Investigator(Renkei-kenkyūsha): TSURUTA HIROKI 神戸大学, 連携創造本部, 准教授 (20346282)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脂質キナーゼ / ジアシルグリセロール / 可視化 / 結合タンパク質 / 細胞内局在変化 / チロシンリン酸化 / フォスファチジン酸 / 細胞周期 / 癌 / ホスファチジン酸

Outline of Final Research Achievements

In this study, molecular mechanism of nuclear-cytoplasm shuttling of diacylglycerol kinase alpha (DGKa) was investigated. We found that RVH-EF region directly bound to C1 domain which functions as nuclear localization signal (NLS) nteraction was enhanced by tyrosin phosphorylation at Y218, resulting weaken the function of C1 domain as NLS. We also identified cyclin dependent kinase 12 and Rheb as binding proteins of DGKa in the nucleus and the cytoplasm, respectively. The former seems to work to stop the cell cycle and the latter seems to contribute the proliferation.

Research Products

• [Journal Article] Amelioration of diabetic nephropathy by oral administration of d-α-tocopherol and its mechanisms (2018)
  • Author(s): Hayashi Daiki、Ueda Shuji、Yamanoue Minoru、Ashida Hitoshi、Shirai Yasuhito
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 82 Issue: 1 Pages: 65-73
  • DOI: 10.1080/09168451.2017.1411184
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase alpha is involved in the vitamin E-induced amelioration of diabetic nephropathy in mice (2017)
  • Author(s): Daiki Hayashi1 Keiko Yagi, Chihong Song, Shuji Ueda, Minoru Yamanoue, Matthew Topham, Toshinobu Suzaki, Naoaki Saito, Noriaki Emoto and Yasuhito Shirai
  • Journal Title: Scientific Repots Volume: 7 Issue: 1 Pages: 2597-2597
  • DOI: 10.1038/s41598-017-02354-3
  • NAID: 120006348186
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of vitamin E and its derivatives on diabetic nephropathy in Rats and identification of diacylglycerol kinase subtype involved in the improvement of diabetic nephropathy (2017)
  • Author(s): Kakehi T, Yagi K, Saito N, Shirai Y
  • Journal Title: Functional Foods in Health and Disease Volume: 7 Pages: 816-832
  • Peer Reviewed / Open Access
• [Journal Article] A novel diacylglycerol kinase α-selective inhibitor, CU-3, induces cancer cell apoptosis and enhances immune response (2015)
  • Author(s): 1)Lui K, Kunii N, Sakuma M, Yamaki A, Mizuno S, Sato M, Sakai H, Kado S, Kumagai K, Kojima H, Okabe T, Nagano T, Shirai Y. and Sakane F
  • Journal Title: J lipid res Volume: ５７ Issue: 3 Pages: 368-379
  • DOI: 10.1194/jlr.m062794
  • Peer Reviewed / Open Access
• [Presentation] ジアシルグリセロールキナーゼalphaの局在及び活性と慢性白血病細胞の増殖に関する研究 (2017)
  • Author(s): 5)山口侑香、木曽裕子、山本麻央、渡辺真以、斎藤尚亮、上田修司、山之上稔、白井康仁
  • Organizer: ConBio2017
• [Presentation] Importance of diacylglycerol kinase alpha activation in the amelioration of diabetic nephropathy (2017)
  • Author(s): Daiki Hayashi
  • Organizer: Kobe University-UC San Diego 3rd Collaborative Symposium (Lipid Enzymes Role in Cancer and Degenerative Diseases)
  • Int'l Joint Research / Invited
• [Presentation] 緑茶カテキンEGCgのメチル化による糖尿病性腎症改善効果の増強 (2017)
  • Author(s): 林大輝, 上田修司, 山之上稔, 芦田均, 白井康仁
  • Organizer: 農芸化学会関西・中四国・西日本支部2017年度合同大阪大会
• [Presentation] ジアシルグリセロールキナーゼalpha活性化剤としての緑茶カテキンEGCgの経口投与による糖尿病性腎症改善効果の検証 (2017)
  • Author(s): 林大輝, 上田修司, 山之上稔, 芦田均, 白井康仁
  • Organizer: 日本農芸化学会2017年度大会
• [Presentation] ジアシルグリセロールキナーゼalphaの核－細胞質間シャトリングの生理的意義の解明 (2016)
  • Author(s): 渡辺真以, 木曽裕子, 上田修司, 山之上稔, 齋藤尚亮, 白井康仁
  • Organizer: 農芸化学会関西支部例会（493回講演会）
  • Place of Presentation: 京都大学 学友会館
  • Year and Date: 2016-02-06
• [Presentation] チロシンリン酸化がジアシルグリセロールキナーゼalphaのドメイン間相互作用及び高次構造に与える影響 (2015)
  • Author(s): 脇阪昌明, 岩下智秋, 濱田大三, 祇園景子, 上田修司, 山之上稔, 鶴田宏樹, 白井康仁
  • Organizer: 農芸化学会関西支部例会（492回講演会）
  • Place of Presentation: 神戸大学農学部
  • Year and Date: 2015-12-05
• [Presentation] ジアシルグリセロールキナーゼalphaの218番目のチロシンリン酸化はドメイン間相互作用と高次構造を変化させる (2015)
  • Author(s): 脇阪昌明, 岩下智秋, 濱田大三, 祇園 景子, 上田修司, 山之上稔, 鶴田宏樹, 白井康仁
  • Organizer: BMB2015
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-12-03
• [Presentation] 細胞内ホスファチジン酸産生を時・空間的に解析できる簡便かつ新規な可視化プローブの開発 (2015)
  • Author(s): 沖本航, 中井寛子, 伊藤俊樹, 森田真也, 上田修司, 山之上稔, 白井康仁
  • Organizer: 第５７回日本脂質生化学会
  • Place of Presentation: 一橋大学一橋講堂
  • Year and Date: 2015-05-29