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2007 Fiscal Year Final Research Report Summary

Patho-physiological analysis of collagen vascular disease development results from dysfunction of the membrane microdomain, lipid rafts

Research Project

Project/Area Number 18591101
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionThe University of Tokyo

Principal Investigator

HONDA Zen-ichiro  The University of Tokyo, Hospital, Lecturer (70238814)

Co-Investigator(Kenkyū-buntansha) TSUCHICYA Naoyuki  Tsukuba University, Institute of Community, Medicine Professor (60231437)
HONDA Hiroaki  Hiroshima University, Department of Developmental Biology, Research Institute for Radiation Biology, Medicine Professor (40245064)
Project Period (FY) 2006 – 2007
KeywordsFcgRIIA / FcgRIIB / transmembrane domain / interface / Lyn / oligomerization
Research Abstract

The findings that FcgRIIB, a prototypical negative regulatory immune receptor, has a common structural polymorphism associated with systemic lupus erythematodes at the transmembrane stretch, and that this polymorphism results in a reduction-of-function receptor, have for the first time prevailed the pivotal role of the negative regulatory receptor family in the immuno-surveillance in humans as well as previously underestimated functional significance of transmembrane domain in immune receptors. This study has been aimed at the structural elucidation of the transmembrane interface developed after the productive oligomerization of immune receptors with polyvalent antigens, immune complexes and stimulatory antibodies, and at the further knowledge of the initiation mechanisms of immune receptor signaling. During the study interval supported by the grant, we have for the first time unveiled that FcgRIIA, a counterpart of FcgRIIB with positive regulatory functions, specifically self associate with one another at the N terminus (outer surface) of the transmembrane stretch, and that this association is in fact productive event: dimerization of the receptor with the aid of disulfide bond mutageneis located at the N-terminus augments Lyn activation, Btk activation and Phospholipase C gamma activation without further ligation of the receotir. This model experiments clearly show that there is a specific, productive interface in immune receotor transmembrane domain, and suggest that the interface serves as a novel therapeutic target for the medicines dissociating the functional interface.

  • Research Products

    (8 results)

All 2008 2007 2006

All Journal Article (8 results) (of which Peer Reviewed: 3 results)

  • [Journal Article] Functional analysis of Src homology 3-encoding exon (exon 2) of p130Cas in primary fib roblasts derived from exon 2-specific knockout mice.2008

    • Author(s)
      Tazaki T, Honda Z, 他
    • Journal Title

      Genes Cells. 13

      Pages: 145-57

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Overexpression / enhanced kinase activity of BCR / ABL and altered expression of Notchl induced acute leukemia in p210BCR / ABL ransgenic mice.2008

    • Author(s)
      Mizuno T, Honda Z, 他
    • Journal Title

      Oncogene (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Successful treatment with infliximab of refractory rheumatoid arthritis in amale with'GDF5 brachydactyly'.2008

    • Author(s)
      Suzuki T, Honda Z.
    • Journal Title

      Rheumatology Int 28

      Pages: 201-3

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Functional analysis of Src homology 3-encoding exon(exon 2) of p 130Cas in primary fibroblasts derived from exon 2-specific knockout mice2008

    • Author(s)
      Takaki T, Honda Z, et. al.
    • Journal Title

      Genes Cells 13(2)

      Pages: 145-57

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Overexpression/enhanced kinase activity of BCR/ABL and altered expression of Notchl induced acute leukemia in p210BCR/ABL transgenic mice2008

    • Author(s)
      Mizuno T, Honda Z, et. al.
    • Journal Title

      Oncogene

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Successful treatment with infliximab of refractory rheumatoid arthritis in a male with 'GDF5 brachydactyly'2007

    • Author(s)
      Suzuki T Honda Z
    • Journal Title

      Rheumatol Int 28(2)

      Pages: 201-3

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Fcepsilon- and Fcgamma-receptor signaling in diseases2006

    • Author(s)
      Honda Z
    • Journal Title

      Springer Semin Immunopathol 28(4)

      Pages: 365-75

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of B cell inhibitory receptor polymorphisms in systemic lupus erythematosus : a negative times a negative makes a positive2006

    • Author(s)
      Tsuchiya N, Honda Z
    • Journal Title

      J Hum Genet 51(9)

      Pages: 741-50

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2010-02-04  

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