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2007 Fiscal Year Final Research Report Summary

Functional analysis of effects of N-glycans on membrane recnpthrs and their associations

Research Project

Project/Area Number 18570177
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionTohoku Pharmaceutical University

Principal Investigator

GU Jianguo  Tohoku Pharmaceutical University, Division of Regulatory Glycobiology, professor (40260369)

Project Period (FY) 2006 – 2007
KeywordsN-Glvcan / glycosyltransferase / integrin / growth factor receptor / signal transduction / laminin
Research Abstract

Glycosylation is involved in a variety of physiological and pathological events, including cell growth, migration, differentiation and tumor invasion. Branched N-glycans, such as bisecting GlcNAc, β1, 6 GlcNAc and core fucose (α1, 6 fucose), are enzymatic products of GnT-III, GnT-V and Fut8, respectively. These branched structures are highly associated with various biological functions of cell adhesion molecules, including cell adhesion and cancer metastasis. We have found Following: 1), α3β1 integrin could be modified by either GnT-III or GnT-V, and GnT-III inhibited GnT-V-stimulated α3β1 integrin-mediated cell migration. The priority of GnT-III for modification of the α3 subunit may explain inhibition of GnT V-induced cell migration by GnT-III. These results were the first to demonstrate that GnT-III and GnT-V competitively modify the same target glycoprotein and that this competition between enzymes either positively or negatively regulates the biological function of the target protein. 2), the role of core fucosylation in α3β1 integrin-mediated events has been studied using Fut8^<+/+> and Fut8^<-/-> embryonic fibroblasts. α3β1 integrin-mediated migration was reduced in Fut8^<-/-> cells. Reintroduction of Fut8 has the potential to reverse such impairments, suggesting that core fucosylation is essential for functional α3β1 integrin. 3), integrins have multiple potential N-glycosylation sites, only N-glycans located on certain motifs regulate integrin conformation and biological function. For example, only N-glycans located on either the β-propeller of α5 integrin contribute to the regulation of integrin function.

  • Research Products

    (49 results)

All 2008 2007 2006

All Journal Article (30 results) (of which Peer Reviewed: 15 results) Presentation (18 results) Book (1 results)

  • [Journal Article] Human REIf-8 is involved in membrane trafficking through early endosomes2008

    • Author(s)
      Fujibayashi, A., et. al.
    • Journal Title

      Cell Struct.Funct (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Branched l-glycans regulate the biological functions of integrins and cadherins2008

    • Author(s)
      Zhao, Y., et. al.
    • Journal Title

      The FEBS Journal (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Functional roles of N-glycans in cell signaling and cell adhesion in cancer2008

    • Author(s)
      Zhao, Y., et. al.
    • Journal Title

      Cancer Sci (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Human REM-8 is involved in membrane trafficking through early endosomes2008

    • Author(s)
      Fujibayashi, A., et. al.
    • Journal Title

      Cell Struct. Funct (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Branched N-glycans regulate the biological functions of integrins and cadherins2008

    • Author(s)
      Zhao, Y., et. al.
    • Journal Title

      The FEBS Journal (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Functional roles of N-glycans in cell signaling and cell adhesion in cancer2008

    • Author(s)
      Zhao, Y., et. al.
    • Journal Title

      Cancer Sci (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Carbohydrate-binding specificity of a fucose-specific lectin from Aspergillus Oryz ae:a novel probe for core fucose2007

    • Author(s)
      Matsumura, K., et. al.
    • Journal Title

      J.Biol.Chem 282

      Pages: 15700-8

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Crystal Structure of Mammalian alphal,6-Fucosyltransferase,FUT82007

    • Author(s)
      Ihara, H., et. al.
    • Journal Title

      Glycobiology 17

      Pages: 455-66

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Introduction of Bisecting GIcNAc in N-glycan of Adenylyl Cyclase III enhances i is activity2007

    • Author(s)
      ILi, W., et. al.
    • Journal Title

      Glycobiology 17

      Pages: 655-62

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Regulation of integrin functions by N-glycans2007

    • Author(s)
      Gu, J.
    • Journal Title

      Yakugaku Zasshi 127

      Pages: 571-578

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Carbohydrate-binding specificity of a fucose-specific lectin from Aspergillus Oryzae : a novel probe for core fucose2007

    • Author(s)
      Matsumura, K., et. al.
    • Journal Title

      J. Biol. Chem 282

      Pages: 15700-8

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystal Structure of Mammalian alpha1, 6-Fucosyltransferase, FUT82007

    • Author(s)
      Ihara, H., et. al.
    • Journal Title

      Glycobiology 17

      Pages: 455-66

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Introduction of Bisecting G1cNAc in N-glycan of Adenylyl Cyclase III enhances its activity2007

    • Author(s)
      Li, W., et. al.
    • Journal Title

      Glycobiology 17

      Pages: 655-62

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of integrin functions by N-glycans2007

    • Author(s)
      Gu, J
    • Journal Title

      Yakugaku Zasshi 127

      Pages: 571-578

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] N-acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyl transferase V on alpha3betal integrin-mediated cell migration2006

    • Author(s)
      Zhao, Y., et. al.
    • Journal Title

      IJ.Biol.Chem 281

      Pages: 32122-30

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] N-glycans on the beta-propeller domain of the integrin alpha5 subunit are essen tial for alpha5betal heterodimerization, expression on the cell surface and its bi ological function2006

    • Author(s)
      Isap, T., et. al.
    • Journal Title

      J.Biol.Chem 281

      Pages: 33258-67

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Deletion of core fucosylation on alpha3betal integrin down-regulates its functions2006

    • Author(s)
      Zhao, Y., et. al.
    • Journal Title

      J.Biol.Chem 281

      Pages: 38343-50

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] A secreted type of p1.6 N-acetylglucosaminiyltransferase V(GnT-V),a novel angiogenesis inducer,is regulated by y-secretase2006

    • Author(s)
      Nakahara, S., et. al.
    • Journal Title

      FASEB J. 20

      Pages: 2451-9

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts2006

    • Author(s)
      Nakagawa, T., et. al.
    • Journal Title

      J.Biol.Chem 281

      Pages: 29797-806

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Phenotype changes of Fut8 knockout mouse:Core fucosylation is crucial for thefunction of growth factor receptors2006

    • Author(s)
      Wang, X., et. al.
    • Journal Title

      Methods Enzymol 417

      Pages: 11-22

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] From glycomics to functional glycomics of sugar chains:identification of target proteins with functional changes using gene targeting mice and knock down cells of FUT8 as examples2006

    • Author(s)
      Kondo, A., et. al.
    • Journal Title

      Biochem.Biophy.Acta 1764

      Pages: 1881-9

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Decoding of Sugar Functions by Identifying Target Glycoproteins2006

    • Author(s)
      Taniguchi, N., et. al.
    • Journal Title

      Current Opinion in Structural Biology 16

      Pages: 561-6

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] N-acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyltransferase V on alpha3betal integrin-mediated cell migration2006

    • Author(s)
      Zhao, Y., et. al.
    • Journal Title

      J. Biol. Chem 281

      Pages: 32122-30

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] N-glycans on the beta-propeller domain of the integrin alpha5 subunit are essential for alpha5beta1 hetero dimerization, expression on cell surface and its biological function2006

    • Author(s)
      Isaji, T., et. al.
    • Journal Title

      J. Biol. Chem 281

      Pages: 33258-67

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Deletion of core fucosylation on alpha3beta1 integrin down-regulates its functions2006

    • Author(s)
      Zhao, Y., et. al.
    • Journal Title

      J. Biol. Chem 281

      Pages: 38343-50

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A secreted type of(β1.6N-acetylglucosaminiyl-transferase V(GnT-V), a novel angiogenesis inducer, is regulated by γ-secretase.2006

    • Author(s)
      Nakahara, S., et. al.
    • Journal Title

      FASEB J 20

      Pages: 2451-9

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts2006

    • Author(s)
      Nakagawa, T., et. al.
    • Journal Title

      J. Biol. Chem 281

      Pages: 29797-806

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Phenotype changes of Fut8 knockout mouse : Core fucosylation is crucial for the function of growth factor receptors2006

    • Author(s)
      Wang, X., et. al.
    • Journal Title

      Methods Enzymol 417

      Pages: 11-22

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] From glycomics to functional glycomics of sugar chains : identification of target proteins with functional changes using gene targeting mice and knock down cells of FUT8 as examples2006

    • Author(s)
      Rondo, A., et. al.
    • Journal Title

      Biochem. Biophy. Acta 1764

      Pages: 1881-9

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Decoding of Sugar Functions by Identifying Target Glycoproteins2006

    • Author(s)
      Taniguchi, N., et. al.
    • Journal Title

      Curr. Opin. Struct. Bio 16

      Pages: 561-6

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] N-結合型糖鎖によるインテグリンとその複合体形成の機能制御2007

    • Author(s)
      顧 建国
    • Organizer
      第30回年日本分子生物学会、第80回生化学会合同会議
    • Place of Presentation
      横浜
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] インテグリンα5におけるN-結合型糖鎖の機能解析2007

    • Author(s)
      佐藤 裕也、伊左 治知弥、福田 友彦、顧 建国
    • Organizer
      第30回年日本分子生物学会、第80回生化学会合同会議
    • Place of Presentation
      横浜
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] N-glycans regulate integrin's functions and its complex formation2007

    • Author(s)
      Jianguo, Gu
    • Organizer
      BMB2007
    • Place of Presentation
      Yokohama
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Functional analysis of alpha5 integrin2007

    • Author(s)
      Yuya, Sato, Tomoya, Isaji, Tomohiko, Fukuda, Jianguo, Gu
    • Organizer
      BMB2007
    • Place of Presentation
      Yokohama
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] N-Acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyl transferase V on a 3 β 1 integrin-mediaged cell migration2007

    • Author(s)
      Jianguo Gu, et. al.
    • Organizer
      XIX International Symposium on Glycoconjugates
    • Place of Presentation
      Cairns,Australia
    • Year and Date
      20070715-20
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] N-Acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyltransferase V on α3β1 integrin-mediaged cell migration.2007

    • Author(s)
      Jianguo, Gu, et. al.
    • Organizer
      XIX International Symposium on Glycoconjugates
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      20070715-20
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Importance of N-glycans on biological functions of integrin2007

    • Author(s)
      Jianguo, Gu
    • Organizer
      The 27th Sapporo Cancer Seminar International Symposium
    • Place of Presentation
      Hokkaido
    • Year and Date
      20070711-13
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Importance of N-glycans on biological functions of integrin2007

    • Author(s)
      Jianguo Gu
    • Organizer
      The 27th Sapporo Cancer Seminar International Symposi um- Glycomics
    • Place of Presentation
      Hokkaido University Confere nce Hall
    • Year and Date
      2007-11-13
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] N-結合型糖鎖によるインテグリンの機能制御2007

    • Author(s)
      顧 建国
    • Organizer
      第80回日本薬理会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-03-14
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] N-glycans regulate the biological functions of integrin2007

    • Author(s)
      Jianguo, Gu
    • Organizer
      80th Japanese pharmacology annual meeting
    • Place of Presentation
      Nagoya
    • Year and Date
      2007-03-14
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] N-Glycan and Integrin2006

    • Author(s)
      Jianguo Gu
    • Organizer
      US-Japan-Europe Glycobiology workshop
    • Place of Presentation
      National Institutes of Health,NIH,USA
    • Year and Date
      2006-09-14
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] N-Glycan and Integrin2006

    • Author(s)
      Jianguo, Gu
    • Organizer
      US-Japan-Europe Glycobiology workshop
    • Place of Presentation
      National Institutes of Health NIH, USA
    • Year and Date
      2006-09-14
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Fut8の機能解析:肺気腫などの疾患におけるコアフコースの役割について2006

    • Author(s)
      顧 建国
    • Organizer
      第26回日本糖質学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2006-08-25
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Functional analysis of Fut82006

    • Author(s)
      Jianguo, Gu
    • Organizer
      26th Japanese Carbohydrate Symposium
    • Place of Presentation
      Sendai
    • Year and Date
      2006-08-25
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] N-Glycans on beta-propeller domain of integrin alpha5 subunit are essential for alpha-beta heterodimeriaation,expression on cell surface and its biological functi ons2006

    • Author(s)
      Tomoya Isaji, Jianguo Gu, Eiji Miyo shi, Naoyuki Taniguchi
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular biology
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-18
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Deletion of core fucosylation on alpha3betal integrin down-regulates its function2006

    • Author(s)
      Yanyang Zhao, Jianguo Gu, Naoyuki Taniguchi
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular biology
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-18
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Core fucosylation regulates EGF receptor-mediated intracellular signaling2006

    • Author(s)
      Xiangchun Wang, Jianguo Gu, Eiji Miyoshi, Koichi Honke, Naoyuki Tan iguchi
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular biology
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-18
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] N-Glycans on beta-propeller domain of integrin alpha5 subunit are essential for alpha-beta heterodimerization, expression on cell surface and its biological functions2006

    • Author(s)
      Tomoya, Isaji, Jianguo, Gu, Eiji, Miyoshi, Naoyuki, Taniguchi
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular biology
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-18
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Comprehensive Glycoscience2007

    • Author(s)
      Yanyang Zhao, et. al.
    • Total Pages
      16
    • Publisher
      Elsevier Ltd
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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