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Molecular regulatory mechanism of cell surface garbohydrate expression and its pathology.

Research Project

Project/Area Number 05454163
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

YAMAOKA Kazuko (1995)  Tokyo Metropolitan Institute of Medical Science, Researcher Dept Biochem.Cell Res., 生命情報研究部門, 研究員 (00124438)

永井 克孝 (1993-1994)  財団法人東京都臨床医学総合研究所, 所長 (80072974)

Co-Investigator(Kenkyū-buntansha) NARA Kiyomitsu  Mitsubishi Kasei Life Science Institute Researcher, 研究員 (40260327)
NAGAI Yoshitaka  Mitsubishi Kasei Life Science Institute Director, 所長 (80072974)
WATANABE Yumiko  Tokyo Metropoliltan Institute of Medical Science, Researcher Dept Biochem.Cell R, 生命情報研究部門, 研究員 (90250216)
KASAHARA Kohji  Tokyo Metropolitan Institute of Medical Science, Researcher Dept Biochem.Cell Re, 生命情報研究部門, 研究員 (60250213)
SANAI Yutaka  Tokyo Metropolitan Institute of Medical Science, Researcher Dept Biochem.Cell Re, 生命情報研究部門, 研究員 (40150289)
梶山 泰生  財団法人東京都臨床医学総合研究所, 生命情報研究部門, 研究員 (70250214)
山岡 和子  財団法人東京都臨床医学総合研究所, 生命情報研究部門, 研究員 (00124438)
小山内 たか  (財)東京都臨床医学総合研究所, 生命情報, 研究員 (60126018)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1994: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1993: ¥3,300,000 (Direct Cost: ¥3,300,000)
Keywordstumor growth factor / galectin / ganglioside / sialyltransferase / genome / 糖脂質 / シアル酸 / 糖転移酵素
Research Abstract

(1) Intramolecular disulfide bonds are essential for the tumor growth factor activity of TGF_<gamma>2 : Amino acid sequence analysis of TGF_<gamma>2 revealed the identity 14Kda galactoside-binding protein (galectin-1) .The TGF_<gamma>2 purified from rat tumor cells, however, showed no sugar-binding activity.To analyze the difference in each activity between TGF_<gamma>2 and galectin-1, we studied the intramolecular disulfide bonds in TGF and galectin-1 by the several methods including chemical clevage of S-S bridge, MOLD-mass spectrometry and affinity chromatography.Several lines of evidences indicated that intramolecular S-S bonds in TFG_<gamma>2 is required for TGF activity and that the lectin activity is induced by thecleavage of S-S bonds in TGF_<gamma>2, possibly as a result of the conformational change.
(2) Molecular cloning, expression and specificity of GD3 synthase : We obtained the cDNA encoding GD3 synthase by the expression cloning strategy.The substrate specificy of the cloned GD3 synthase showed that this enzyme synthesizes not only GD3, but GQ1b which was believed by the other sialyltransferase, SAT5.These results suggest this enzyme play a key role in the regulation of ganglioside expression in CNS.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kiyomitsu Nara: "Expression Cloning of a CMP-NeuAc: NeuAcα2,3 Galβ1-4Glcβ1.1'Cer α2、8-Sialyltransferase(Go3 Synthase) from Human Melanoma Cells" Proc. Natl. Acad. Sci. USA. 91. 7952-7956 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoichi Matsuda: "Chromosome Mapping of the GD3 Spnthase (SlAT8) in Human and Mouse" Genomics. 32. 137-139 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasumaru Hatanaka: "A Carbene-generating biotinylated lactosylceramide analog as novel photoreactive substrate for GM3 synthase" Bioorg Med. Chem. Lett. 5. 2859-2862 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasumaru Hatanaka: "Synthesis of a carbene-linked CMP-NANA analog and its inbibitory effects on GM3 and GD3 synthase" Heterocycles. 43. 531-534 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazuko Yamaoka: "Stouctural and functional characterization of a novel tumor derived rat galectin-1 having transforming growth factor(TGF) activity" J. of Biochemistry. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kiyomitsu Nara: "Acceptor substrate specificity of a cioned GD3 Synthase that catalyses the biosynthesis of both GD3 and GDlC/Grla/GQib" Eur. J. Biochem.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] NARA,K.: ""Expression cloning of a CMP-NeuAc : NeuAcalpha2,3 Galbeta1,4Glcbeta1,1'Cer alpha2,8-Sialyltransferase (GD3 Synthase) from Human Melanoma Cells."" Proc.Natl.Acad.Sci.USA. 91. 7952-7956 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsuda, Y.: ""Chromosome Mapping of the GD3 Synthase Gene in Man and Mouse." Genomics. 32. 137-139 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hatanaka, Y.: ""A Carbene-generating Biotinylated Lactosylceramide Analog as Novel Photoreactive Substrate for GM3 Synthase."" Bioorg.Med.Chem.Lett. 2859-2862 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hatanaka, Y.: ""Synthesis of a carbone-linked CMP-NANA analog and its inhibitory effects on GM3 and GD3 synthase." Heterocycles. 43(3). 531-534 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamaoka, K.: ""Structural and functional characterization of a novel trmor-derived rat galectin-1 having transforming growth factor (TGF) activity : Intermolecular disulfide bridges are indispensable for TGF activity."" J.Biochem. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nara K.: ""Acceptor Substrate Specificity of Cloned GD3 Synthase, which Catalyzes the Biosynthesis of Both GD3 and GD1c/GT1a/GQ1b"" Eur.J.Biochem. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] YOICHI MATSUDA: "Chromosome Mapping of the GD3 synthase(SIAT8)in Human and Mouse" Genomics. 32. 137-139 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] YAsumaru Hatanaka: "A Carbene-generating biotinylated lactosylceramide analog as novel photoreactive substrate for GM3 synthase" Bioorg. Med. Chem. Lett. 5. 2859-2862 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] YAsumaRu HATANAKA: "Synthesis of a carbone-linked CMP-NANA analog and its inhibitory effects on GM3 and GD3 synthase" Heterocycles. 43. 531-534 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] KAZUKO YAMAOKA: "Structural and functional characterization of a novel tumorderived rat galectin-1 having transforming growth factor(TGF)activity" J. of Biochemistry. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kiyomitsu NARA: "Acceptor substrate specificity of a cloned GD3 synthase that catalyzes the biosynthesis of both GD3 and GD1c/GT1a/GQ1b" Eur. J. of BIochemistry. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hidari,K.I.J.P.: "In vitro synthesis of disialoganglioside(GD1alpha) from asialo-GM1 using sialyltransferase" Eur.J.Biochem.221. 603-609 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kasahara,K.: "Enzymatic assay of glycolipid sialyltransferase using reverse-phase TLC" Anal.Biochem.218. 224-226 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nara,K.: "Expression cloning of a CMP-NeuAc:GM3 alpha2,8 sialyltransfarase from human melanoma cells" Proc.Natl.Acad.Sci.USA. 91. 7952-7956 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hidari,K.I.J.P.: "A unique biosynthetic pathway for gangliosides exist in Xenopus laevis oocytes" FEBS letters. 353. 25-28 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kohji Kasahara: "Enzymatic Assay of Glycosphingolipid Sialyltransferase" Analytical Biochemistry. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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