• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2006 Fiscal Year Final Research Report Summary

Scenario of the biosynthesis of glycosaminoglycans

Research Project

Project/Area Number 14082207
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHokkaido University (2006)
Kobe Pharmaceutical University (2002-2005)

Principal Investigator

SUGAHARA Kazuyuki  Hokkaido University, Faculty of Advanced LifeScience, Professor (60154449)

Project Period (FY) 2002 – 2006
Keywordschondroitin sulfate / heparan sulfate / chondroitin synthase / proteoglycan / chondroitin polymerizing factor / glycosyltransferase / EXT tumor suppressor gene / glycosaminoglycan
Research Abstract

Sulfated glycosaminoglycans, which are side polysaccharide chains of proteoglycans, can be largely classified into a heparan sulfate type and a chondroitin sulfate type, and regulate functions of a wide variety of signaling protein molecules. However, the biosynthetic mechanism of these glycans had not been well understood before this project was launched. Therefore, the aim of this project was to clarify the scenario of the biosynthesis of sulfated glycosaminoglycans. During the project period, we clarified various aspects of the biosynthetic mechanism including the chain initiation, elongation, polymerization and the regulation of the chain length using the in vivo and in vitro systems of human, fly and nematode, and accomplished the aim of the project. The results included identification of glycosyltransferases, sulfotransferases and regulatory factors as well as molecular interactions of these ensymes and factors. Furthermore, it was demonstrated that chondroitin is essential in the cell division of C. elegans by the RNAi approach using the RNAs of the chondroitin synthase and the chondroitin polymerizing factor of the namatode. A human genetic disease caused by a deficiency of a chondroitin 6-O-sulfotransferase was discovered. On the other hand we clarified the molecular mechanism whereby the neurite outgrowth of mouse hippocampal neurons is promoted by pleiotrophin and hepatocyte growth factor through specific interactions with chondoitin sulfate chains in the extracellular matrices. It was also proved that chondroitin sulfate plays a role as a receptor for virus infection. The sugar sequences required for the interactions with a growth factor pleiotrohin and a few cytokines were also revealed. These results have started influencing considerably not only the glycobiology field but also other related fields. The on-going analysis of the GlcAT-I-KO and EXTL2-KO-mice will also confirm the importance of the functions of these sulfated glycosaminoglycan chains.

  • Research Products

    (33 results)

All 2007 2006 2005 2004 2003 2002

All Journal Article (25 results) Book (3 results) Patent(Industrial Property Rights) (5 results)

  • [Journal Article] Expression of rib-l, a Caenorhabditis elegans Homolog of the Human TumorSuppressor EXT Genes is indispensable for heparan sulfate synthesis and embryonic morphogenesis.2007

    • Author(s)
      Kitagawa, H.
    • Journal Title

      J. Biol. Chem. 282

      Pages: 8533-8544

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of rib-1, a Caenorhabditis elegans Homolog of the Human Tumor Suppressor EXT Genes is indispensable for heparan sulfate synthesis and embryonic morphogenesis.2007

    • Author(s)
      Kitagawa, H., Izumikawa, T., Mizuguchi, S., Dejima, K., Nomura, K. H., Egusa, N., Taniguchi, F., Tamura, J., Gengyo-Ando, K., Mitani, S., Nomura, K., Sugahara, K.
    • Journal Title

      J. Biol. Chem. 282 (11)

      Pages: 8533-8544

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Biosynthesis ofglycosaminoglycans and proteoglycans.2007

    • Author(s)
      Uyama, T., Kitagawa, H., Sugahara, K.
    • Journal Title

      Comprehensive Glycoscience (Kamerling J. P., ed. ) Elsevier (Amsterdam) vol. 3, 25

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Heparan sulfate polymerization in Drosophila.2006

    • Author(s)
      Izumikawa, T.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 1929-1934

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] C. elegans pharyngeal morphogenesis requires both de novo synthesis of pyrimidines and synthesis of heparan sulfate proteoglycans.2006

    • Author(s)
      pranks, DM.
    • Journal Title

      Dev, Biol. 296

      Pages: 409-420

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Heparan sulfate polymerization in Drosophila.2006

    • Author(s)
      Izumikawa, T., Egusa, N., Taniguchi, F., Sugahara, K., Kitagawa, H.
    • Journal Title

      J. Biol. Chem. 281 (4)

      Pages: 1929-1934

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] G. C. elegans pharyngeal morphogenesis requires both de novo synthesis of pyrimidines and synthesis of heparan sulfate proteoglycans2006

    • Author(s)
      Franks, D. M., Izumikawa, T., Kitagawa, H., Sugahara, K., Okkema, P.
    • Journal Title

      Dev. Biol. 296 (2)

      Pages: 409-420

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Demonstration of the pleiotrophin-binding oligosaccharide sequences isolatedfrom chondroitin sulfate/dennatan sulfate hybrid chains of embryonic pig brains.2005

    • Author(s)
      Bao, X.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 35318-35328

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Demonstration of the pleiotrophin-binding oligosaccharide sequences isolated from chondroitin sulfate/dermatan sulfate hybrid chains of embryonic pig brains.2005

    • Author(s)
      Bao, X., Muramatsu, T., Sugahara, K.
    • Journal Title

      J. Biol. Chem. 280 (42)

      Pages: 35318-35328

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Biosynthesis of heparin and heparan sulfate.2005

    • Author(s)
      Mizumoto, S., Kitagawa, H., Sugahara, K.
    • Journal Title

      Chemistry and Biology of Heparin and Heparan sulfate (Garg, H. G., Linhardt, R. J., and Hales, C. A., eds. ), Elsevier, Oxford, UK. 40

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Loss of chondroitin 6-O-sulfotransferase-l function results in severe human chondrodysplasia with progressive spinal involvement.2004

    • Author(s)
      Thiele, H.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 101

      Pages: 10155-10160

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nematode chondfoitin polymerizing factor showing cell/organ-specific expression is indispensable for chondroitin synthesis and embryonic cell division.2004

    • Author(s)
      Izumikawa, T.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 53755-53761

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement.2004

    • Author(s)
      Thiele, H., Sakano, M., Kitagawa, H., Sugahara, K,. Rajab, A., Hohne, W., Leschik, G, Nurnberg, P., Mundlos, S.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 101 (27)

      Pages: 10155-10160

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nematode chondroitin polymerizing factor showing cell/organ-specific expression is indispensable for chondroitin synthesis and embryonic cell division.2004

    • Author(s)
      Izumikawa, T., Kitagawa, H., Mizuguchi, S., Nomura, K. H., Nomura, K., Tamura, J., Gengyo-Ando, K., Mitani, S., Sugahara, K.
    • Journal Title

      J. Biol. Chem. 279 (51)

      Pages: 53755-53761

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular cloning and expression of a second chondroitin N-acetylgalactosaminyltransferase involved in the biosynthetic initiation and elongation of chondroitin/dennatan sulfate.2003

    • Author(s)
      Uyama, T.
    • Journal Title

      J. Biol. Chem. 278

      Pages: 3072-3078

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Crystal structure of an 1, 4-N-acetylhexosammyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfatebiosynthesis.2003

    • Author(s)
      Pedersen, L. C.
    • Journal Title

      J. Biol. Chem 278

      Pages: 14420-14428

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Heterogeneity of the chondroitin sulfate portion of phosphacan/6B4 prbteoglycan regulates its binding affinity for pleiotrophin/HB-GAM.2003

    • Author(s)
      Maeda, N.
    • Journal Title

      J, Biol. Chem. 278

      Pages: 35805-35811

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Recent advances in the structural biology of chondroitin sulfate and dermatan sulfate2003

    • Author(s)
      Sugahara, K.
    • Journal Title

      Curr. Opin. Struct. Biol. 13

      Pages: 612-620

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular cloning and expression of a second chondroitin N-acetylgalactosaminyltransferase involved in the biosynthetic initiation and elongation of chondroitin/dermatan sulfate.2003

    • Author(s)
      Uyama, T., Kitagawa, H., Tanaka, J., Tamura, J., Ogawa, T., Sugahara K
    • Journal Title

      J. Biol. Chem. 278 (5)

      Pages: 3072-3078

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystal structure of an 1, 4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis.2003

    • Author(s)
      Pedersen, L. C., Dong, J., Taniguchi, F., Kitagawa, H., Krahn, J., Pedersen, L. G., Sugahara, K., Negishi, M.
    • Journal Title

      J. Biol. Chem. 278 (16)

      Pages: 14420-14428

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Heterogeneity of the chondroitin sulfate portion of phosphacan/6B4 proteoglycan regulates its binding affinity for pleiotrophin/HB-GAM.2003

    • Author(s)
      Maeda, N., He, J., Yajima, Y, Mikami, T., Sugahara. K., Yabe, T.
    • Journal Title

      J. Biol. Chem. 278 (37)

      Pages: 35805-35811

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Recent advances in the structural biology of chondroitin sulfate and dermatan sulfate2003

    • Author(s)
      Sugahara, K., Mikami, T., Uyama, U., Mizuguchi, S., Nomura, K., Kitagawa, H.
    • Journal Title

      Curr. Opin. Struct. Biol. 13(5)

      Pages: 612-620

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Recognition of glycosaminoglycans by midkine.2003

    • Author(s)
      Muramatsu, T., Muramatsu, H., Kaneda, N., Sugahara, K.
    • Journal Title

      Methods in Enzymol., (Lee, Y. C., and . Lee R. T. eds. ), Academic Press, New York 363

      Pages: 11

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Oversulfated chondroitiin/dermatan sulfates containing GlcA 1/IdoA 1-3GalNAc(4, 6-O-disulfate)interact with L- and P-selectin and chemokines.2002

    • Author(s)
      Kawashima, H
    • Journal Title

      J. Biol. Chem. 277

      Pages: 12921-12930

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Oversulfated chondroitin/dermatan sulfates containing GlcA 1/IdoA 1-3GalNAc(4, 6-O-disulfate)interact with L- and P-selectin and chemokines.2002

    • Author(s)
      Kawashima, H., Atarashi, K., Hirose, M., Hirose, J., Yamada, S., Sugahara, K., Miyasaka, M.
    • Journal Title

      J. Biol. Chem. 277 (15)

      Pages: 12921-12930

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Comprehensive Glycoscience (Kamerling J. P., ed. )2007

    • Author(s)
      Uyama, T.
    • Total Pages
      25
    • Publisher
      Elsevier (Amsterdam)
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Chemistry and Biology of Heparin and Heparan sulfate (Garg, H. G・, Linhardt, R. J・, and Hales, C. A・, eds・)2005

    • Author(s)
      Mizumoto, S
    • Total Pages
      40
    • Publisher
      Elsevier, Oxford, UK.
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Methods in Enzymol. (Lee, Y. C., and . Lee R. T. eds. )2003

    • Author(s)
      Muramatsu, T.
    • Total Pages
      11
    • Publisher
      Academic Press, New York
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] グリコサミノグリカン糖鎖の生合成不全マウス2007

    • Inventor(s)
      北川裕之, 菅原一幸, 浅野雅秀, 杉原一司
    • Industrial Property Rights Holder
      JSTおよび国立大学法人金沢大学
    • Industrial Property Number
      特願2007-34346
    • Acquisition Date
      2007-02-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] プレイオトロフィン結合性および非結合性のコンドロイチン硫酸/デルマタン硫酸オリゴ糖2005

    • Inventor(s)
      菅原 一幸, バオシンフオン
    • Industrial Property Rights Holder
      (財)新産業創造研究機構(TLOひようご)
    • Industrial Property Number
      特願2005-197587特開2006-16099
    • Filing Date
      2005-07-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] ヘパラン鎖のin vitro合成法とその利用2004

    • Inventor(s)
      菅原一幸, 北川裕之, 金 炳澤
    • Industrial Property Rights Holder
      (財)新産業創造研究機構(TLOひようご)
    • Industrial Property Number
      PCT/JP20O4/007243 ; W02004/104208
    • Filing Date
      2004-05-20
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] Molecular ckning and characterization of a novel chond-oitin polymenzing factor, which cooperates with chondroitin synthase for chondoroitin polymnerization2003

    • Inventor(s)
      菅原 一幸, 北川裕之
    • Industrial Property Rights Holder
      (財)新産業創造研究機構(TLOひようご)
    • Industrial Property Number
      Application No. 60/453, 425 ; WO2004/078969
    • Filing Date
      2003-03-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] Cone protein sequences of primer subsuales in additon to theEXTI-EXT2 interaction are essential for polymnenzation of a heparan sulfate/heparin precusor heparan2003

    • Inventor(s)
      菅原 一幸, 北川 裕之, 金 炳澤
    • Industrial Property Rights Holder
      (財)新産業創造研究機構(TLOひようご)
    • Industrial Property Number
      Application No. : 60/473, 165
    • Filing Date
      2003-05-23
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2010-06-09  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi