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1995 Fiscal Year Final Research Report Summary

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

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)
Project Period (FY) 1993 – 1995
Keywordstumor growth factor / galectin / ganglioside / sialyltransferase / genome
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.

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1997-03-04  

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