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スフィンゴシン1-リン酸とその受容体の情報伝達機構と生理機能の解析

Research Project

Project/Area Number 12140201
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHokkaido University

Principal Investigator

五十嵐 靖之  北海道大学, 大学院・薬学研究科, 教授 (70091965)

Co-Investigator(Kenkyū-buntansha) 木原 章雄  北海道大学, 大学院・薬学研究科, 助教授 (50333620)
光武 進  北海道大学, 大学院・薬学研究科, 助手 (10344475)
矢冨 裕  東京大学, 大学院・医学系研究科, 教授 (60200523)
岡島 史和  群馬大学, 生体調節研究所, 教授 (30142748)
井ノ口 仁一  北海道大学, 大学院・薬学研究科, 助教授 (70131810)
和田 淳  北海道大学, 大学院・薬学研究科, 助手 (00301953)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥131,100,000 (Direct Cost: ¥131,100,000)
Fiscal Year 2004: ¥32,400,000 (Direct Cost: ¥32,400,000)
Fiscal Year 2003: ¥32,400,000 (Direct Cost: ¥32,400,000)
Fiscal Year 2002: ¥32,300,000 (Direct Cost: ¥32,300,000)
Fiscal Year 2001: ¥34,000,000 (Direct Cost: ¥34,000,000)
Keywordsスフィンゴ脂質 / 糖脂質 / セラミド / スフィンゴシン1-リン酸 / シグナル伝達 / アポトーシス / 細胞膜ミクロドメイン / 細胞内脂質輸送 / Edg受容体 / スフィンゴシンキナーゼ / G蛋白質
Research Abstract

スフィンゴ脂質のシグナル機構や受容体の研究で五十嵐班はこの1年間で,48報の原著論文を発表するなど大きな成果を上げた。特に主立った成果として(1)ヒトスフィンゴ脂質C-4水酸化酵素hDES2を始めてクローニングした(FEBS Lett,2004) (2)マスト細胞で抗原刺激での顆粒球放出にセラミドキナーゼが関与していることを明らかにした(JBC,2004) (3)酵母細胞膜の非対称性維持機構の存在,特にスフィンゴ脂質とグリセロリン脂質のクロストーク機構の存在を初めて示した(MBC,2004) (4)哺乳類スフィンゴ脂質代謝のうちで最後まで残されていた3-ケトヒドロキシスフィンゴシン還元酵素(FTV-1)のクローニングに成功した(JBC,2004) (5)酵母細胞スフィンゴシンキナーゼのリン酸化機構とその分解における役割を明らかにした(JBC,2004) (6)日米共同研究でEDG-6とS1Pの結合機構を分子モデルを使って示した(BJ、2005) (7)スフィンゴシンキナーゼ2の特異的阻害剤を合成開発した(BMC,2005)などの成果をあげている。

Report

(5 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (35 results)

All 2005 2004 Other

All Journal Article (6 results) Publications (29 results)

  • [Journal Article] Phosphorylation by Pho85 cyclin-dependent kinase acts as a signal for the down-regulation of the yeast sphingoid long-chain base kinase Lcb4 during the stationary phase.2005

    • Author(s)
      Iwaki S.
    • Journal Title

      J.Biol.Chem. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Sphingosine-1-Phosphate Analog Recognition and Selectivity at S1P4 within the Endothelial Differentiation Gene Family of Receptors.2005

    • Author(s)
      Inagaki Y.
    • Journal Title

      Biochem.J. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation.2004

    • Author(s)
      Mizutani Y.
    • Journal Title

      FEBS Lett. 563

      Pages: 93-97

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ceramide kinase is a mediator of calcium-dependent degranulation in mast cells.2004

    • Author(s)
      Mitsutake S.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 17570-17579

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cross talk between sphingolipids and glycerophospholipids in the establishment of plasma membrane asymmetry2004

    • Author(s)
      Kihara A.
    • Journal Title

      Mol.Biol.Cell 15(11)

      Pages: 4949-4959

    • Related Report
      2004 Annual Research Report
  • [Journal Article] FVT-1 is a mammalian 3-ketodihydrosphingosine reductase with an active site that faces the cytosolic side of the endoplasmic Reticulum Membrane.2004

    • Author(s)
      Kihara A.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 49243-49250

    • Related Report
      2004 Annual Research Report
  • [Publications] Kohno T.: "Truncation of the N-terminal ectodomain has implications in the N-glycosylation and transport to the cell surface of Edg-1 / S1P1 receptor"J.Biochem.. 134(5). 667-673 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kohno T.: "Sphingosine 1-phosphate promotes cell migration through the activation of Cdc42 in Edg-6/S1P4-expressing cells"Genes to Cells. 8. 685-697 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Meacci E.: "Down-regulation of Edg5/S1P2 during myogenic differentiation results in the 131. specific uncoupling of sphingosine 1-phosphate signaling via phospholipase D"Biochem.Biophys.Acta.. 1633(3). 133-142 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Uemura: "Csg1p and newly identified Csh1p function in mannosylinositol phosphorylceramide synthesis by interacting with Csg2p"J.Biol.Chem.. 278(46). 45049-45055 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Inagaki Y.: "Identification of functional nuclear export sequences in human sphingosine kinase 1"Biochem.Biophys.Res.Commun.. 311(1). 168-173 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Fukuda: "Identification of PECAM-1 association with sphinogosine kinase 1 and its regulation by agonist-induced phosphorylation"Biochem.Biophys.Acta.. 1636(1). 12-21 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sano T.: "Novel mechanism for lysophosphatidic acid production involving activated platelets"J. Biol. Chem.. 277・24. 21197-21206 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chun J.: "International Union of Pharmacology. XXXIV. Lysophospholipid Receptor Nomenclature"Phaimacol. Rev.. 54. 265-269 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kihara A.: "Identification and characterization of a saccharomyces cerevisiae gene, RSB1, involved in sphingoid long-chain base release"J. Biol. Chem.. 277. 30048-30054 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogawa C.: "Identification and characterization of a novel human sphingosine 1-phosphate phosphohydrolase, hSPP2"J. Biol. Chem.. 278. 1268-1272 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kohno T.: "N-glycans of sphingosine-1-phosphate receptor Edg1 regulate ligand-induced receptor internalization"FASEB J.. 16. 983-992 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tagami S.: "Ganglioside GM3 participates inthe pathological conditions of insulin resistance"J. Biol. Chem.. 277. 3085-3092 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kihara A.: "Transmembrane topology and functions of sphingoid long-chain 1-phosphate phosphatase"Gene to Cells. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kihara A.: "Sphingosine 1-phosphate lyase, SPL, is involved in differentiation of F9 embryonal carcinoma cells toward promitive endoderm"J. Biol. Chem.. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hakogi T.: "Synthesis of fluorescence-labeled sphingosineand sphingosine 1-phosphate : an potential tool fro the sphingosine 1-phosphate behavior"Bioorg. Med. Chem Lett.. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yutaka Yatomi: "Sphingosine 1-phosphate : synthesis and release"Prostaglandins & other Lipid Mediators. 64. 107-122 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takashi Murate: "Cell Type-specific Localization of Sphingosine Kinase la in Human Tissues"The Journal of Histochemistry & Cytochemistry. 49(7). 845-855 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuya Kabayama: "Suppression of Integrin Expression and Tumorigenicity by Sulfation of Lactosylceramide in 3LL Lewis Lung Carcinoma Cells"The Journal of Biological Chemistry. 276(29). 26777-26783 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Seiichi Tagami: "Ganglioside GM3 Participates in the Pathological Conditions of Insurin Resistance"The Journal of Biological Chemistry. 277(5). 3085-3092 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takayuki Kohno: "N-glycans of Sphingosine 1-phosphate Receptor, Edg-1, Regulate Ligand Induced Receptor Internalization"FASEB Journal. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takamitsu Sano: "Multiple Mechanisms Linked to Platelet Activation Result in Lysophosphatidic Acid and Sphingosine-1-Phosphate Generation in Blood"The Journal of Biological Chemistry. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yutaka Yatomi: "Sphingosine 1-Phosphate Breakdown in Platelets : A Novel Pathway for Formation of Sphingolipid Mediators"The Journal of Biological Chemistry. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 五十嵐靖之 他編: "マイクロドメイン形成と細胞のシグナリング:スフィンゴ脂質の新しい生物機能"共立出版株式会社. 258 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sano,T.: "Novel mechanosm for lysophosphatidic acid production involving activated platelets."J.Biol.Chem.. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kohno T.: "Aspargine-linked glycosylation of Edg1, a receptor for sphingosine 1-phosphate : Significance in receptor internalization and receptor-coupled signaling."J.Biol.Chem.. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yatomi Y.: "Sphingosine 1-phosphate as a major bioactive lysophospholipid released from platelets and interacting with endothelial cells."Blood. 96. 3431-3438 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inokuchi J.: "Glycosphingolipid deficiency affects functional microdomain formation in Lewis lung carcinoma cells."Glycoconjugate J.. 17. 239-245 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Motohashi K.: "Identification of lysophospholipid receptors in human platelets : the relation of two agonists, lyso-phosphatidic acid and sphingosine 1-phosphate."FEBS Lett.. 468. 189-193 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamamura S.: "Sphingosine1-phosphate inhibits haptotactic motility by overproduction of focal adhesion site in B16 melanoma cells through Edg-induced activation of Rho."Ann.N.Y.Acad Sci. 905. 301-307 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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