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Studies on Biosynthetic Mechanism of the Sulfated Glycosaminoglycans

Research Project

Project/Area Number 14572086
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKobe Pharmaceutical University

Principal Investigator

KITAGAWA Hiroshi  Kobe Pharmaceutical Univ., Associate Professor, 薬学部, 助教授 (40221915)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsGlycosyltransferases / chondroitin Sulfate / Heparan Surfate / Glycosaminoglycans / Proteoglycan / tumor suppressor Gene / C.elegans / Crystal Structure / グルクロン酸 / cDNAクローニング / 細胞外マトリックス
Research Abstract

Sulfated glycosaminoglycans including heparin/heparan sulfate and chondroitin/dermatan sulfate have been implicated in numerous pathophysiological phenomena of vertebrates and invertebrates. To facilitate analyses of the functions of these glycosaminoglycans through gene manipulation in various model animals, we have cloned several genes encoding the glycosyltransferases and sulfotransferase required for the biosynthesis of the glycosaminoglycans. In this study, we cloned additional six genes encoding the glycosyltransferases and a related protein involved in glycosaminoglycan biosynthesis and found novel functions of chondroitin in Caenorhabditis elegans as follows.
1)Molecular cloning of human chondroitin N-acetylgalactosaminyltransferase-2(GalNAcT-2) :
We identified a novel human chondroitin GalNAcT, designated chondroitin GalNAcT-2. GalNAcT-2 transferred β1,4-N-acetylgalactosamine(GalNAc) from UDP-[^3H]GalNAc not only to a polymer chondroitin representing growing chondroitin, but als … More o to GlcUAβ1-3Galβ1-O-C2H4NHCbz, a synthetic substrate for β-GalNAc transferase I that transfers the first GalNAc to the core tetrasaccharide in the protein-linkage region of chondroitin sulfate.
2)Molecular cloning of three Drosophila glucuronyltransferases :
We cloned and characterized three Drosophila β1,3-glucuronytransferases. The results showed that all of them are likely involved in the synthesis of the glycosaminoglycans-protein linkage region in Drosophila.
3)cDNA cloning of C.elegans chondroitin synthase and demonstration of novel functions :
We cloned a chondroitin synthase homologue of C.elegans and depleted expression of its product by RNA-mediated interference. We found that blocking chondroitin synthesis results in cytokinesis defects in early embryogenesis.
4)Molecular cloning of a chondroitin polymerizing factor :
We previously cloned human chondroitin synthase, but chondroitin polymerization was not demonstrated in vitro using the recombinant chondroitin synthase. We reported that the chondroitin polymerizing activity requires concomitant expression of a novel protein designated chondroitin polymerizing factor with chondroitin synthase.
5)In vitro heparan sulfate polymerization :
We found that the core protein moieties in addition to the interaction between EXT1 and EXT2 are required for heparan sulfate polymerization. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 守山徹他: "Molecular cloning and expression of a second chondroitin N-acetylgalactosaminyltransferase involved in the initiation and elongation ・・・"J.Biol.Chem.. 278. 3072-3078 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim Byung-Taek他: "Identification and characterization of three Drosophila melanogaster glucuronyltransferases responsible for the Synthesis of the ・・・"J.Biol.Chem.. 278. 9116-9124 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Pedersen, L.C. 他: "Crystal Structure of an 1,4-N-acetylhexosaminyltransferase (EXTL2) member of the exostosin gene family involved ・・・"J.Biol.Chem.. 278. 14420-14428 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 水口惣平 他: "Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans"Nature. 423. 443-448 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 北川裕之 他: "Molecular cloning of a chondroitin polymerizing factor ・・・"J.Biol.Chem.. 278. 23666-23671 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim Byung-Taek他: "In Vitro heparan Sulfate polymerization : Crucial roles of core ・・・"J.Biol.Chem.. 278. 41618-41623 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toru Uyama, Hiroshi Kitagawa, Junko Tanaka, Jun-ichi Tamura, Kazuyuki Sugahara: "Molecular cloning and expression of a second chondroitin N-acetylgalactosaminyltransferase involved in the initiation and elongation of chondroitin/dermatan sulfate."J.Biol.Chem.. 278(5). 3072-3078 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Byung-Taek Kim, Kazunori Tsuchida, John Lincecum, Hiroshi Kitagawa, Merton Bernfield, Kazuyuki Sugahara: "Identification and characterization of three Drosophila melanogaster glucuronyltransferases responsible for the synthesis of the conserved glycosaminoglycan-protein linkage region of proteoglycans : Two novel homologs exhibit broad specificity towards oligosaccharides from proteoglycans, glycoproteins and glycosphingolipids."J.Biol.Chem.. 278(11). 9116-9124 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lars C.Pedersen, Jian Dong, Fumiyasu Taniguchi, Hiroshi Kitagawa, Joe M.Krahn, Lee G.Pedersen, Kazuyuki Sugahara, Masahiko Negishi: "Crystal structure of an α1,4-N-acetylhexosaminyltransferase(EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis."J.Biol.Chem.. 278(16). 14420-14428 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Souhei Mizuguchi, Toru Uyama, Hiroshi Kitagawa, Kazuko H.Nomura, Katsufumi Dejima, Keiko Gengyo-Ando, Souhei Mitani, Kazuyuki Sugahara, Kazuya Nomura: "Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans."Nature. 423(6938). 443-448 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiroshi Kitagawa, Tomomi Izumikawa, Toru Uyama, Kazuyuki Sugahara: "Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization."J.Biol.Chem.. 278(26). 23666-23671 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Byung-Taek Kim, Hiroshi Kitagawa, Junko Tanaka, Jun-ichi Tamura, Kazuyuki Sugahara: "In vitro heparan sulfate polymerization : Crucial roles of core protein moieties of primer substrates in addition to the EXT1/EXT2 interaction."J.Biol.Chem.. 278(43). 41618-41623 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Pedersen, L.C., 北川裕之 他: "Crystal structure of an α1,4-N-acetylhexosaminyltransferase (EXTL2),a member of the exostosin gene family involved in heparan sulfate biosynthesis."J.Biol.Chem.. 278・16. 14420-14428 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 水口惣平, 宇山徹, 北川裕之 他: "Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans."Nature. 423・6938. 443-448 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 北川裕之 他: "Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization."J.Biol.Chem.. 278・26. 23666-23671 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kim, B.T., 北川裕之 他: "In vitro heparan sulfate polymerization : Crucial roles of core protein moieties of primer substrates in addition to the EXT1/EXT2 interaction."J.Biol.Chem.. 278・38. 36115-36127 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 宇山徹, 北川裕之 他: "Molecular Cloning and Expression of a Second Chondroitin N-Acetylgalactosaminyltransferase Involved in the Initiation and Elongation of Chondroitin/Dermatan ・・・"J. Biol. Chem.. 278・5. 3072-3078 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kim Byung-Taek, 北川裕之 他: "Identification and Characterization of Three Drosophila melanogaster Glucuronyltransferases Responsible for the Synthesis of the Conserved ・・・"J. Biol. Chem.. 278・11. 9116-9124 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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