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1993 Fiscal Year Final Research Report Summary

FcepsilonRI-mediated signal transduction

Research Project

Project/Area Number 04454212
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionJuntendo University School of Medicine

Principal Investigator

RA Chisei  Dept.Immunol., Juntendo Univ.School, Med., Assoc.Pro., 医学部, 講師 (60230851)

Co-Investigator(Kenkyū-buntansha) HIROSE Tomohiro  Cent.Res.Labo., Yamanouchi Phamaceutical Co., Reserch Staff., 中央研究所, 研究員
Project Period (FY) 1992 – 1993
KeywordsFcepsilonRI / Signal transduction / Mast cell / Chimerie molecule / Syk kinase
Research Abstract

The high affinity receptor for IgE (FcepsilonRI) is selectively expressed on mast cells, basophils, eosinophils and Langerhans cells in the skin and triggers allergic reaction. FcepsilonRI has a tetrameric structure consisting of one alpha, one beta and two gamma chains of which alpha chain binds IgE specifically and beta, gamma chains transduce signals from cell membrane into cytoplasm for cellular activation. Recombinant gene technique had enabled us to generate soluble human FcepsilonRIalpha exodomain as a secreting form (soluble alpha) from CHO cells. In order to elucidate molecular mechanisms of high affinity binding between IgE and FcepsilonRIalpha, we have to know the tertiary structure of IgE binding site on alpha chain. We succeeded in the production of soluble alpha in a large amount by baculo virus system and identified the sugar binding sites and the extent of bound-sugar at each site. For the crystallization of soluble alpha to analyze the tertiary structure of IgE binding site, we are now introducing mutations of amino acids to remove sugar in soluble alpha.
We constructed chymeric molecules composed of human FcepsilonRI alpha chain exodomain and intracellular domain of FcepsilonRI beta or gamma chain and introduced them into different kind of cell lines to analyze IgE-mediated signal transduction through a simpler single molecule. In the meantime, we cloned human Syk kinase gene and are now trying to introduce this gene into the chimeric molecule expressing transfectants to analyze the role of this kinase in FcepsilonRI-mediated signal transduction.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Ra,C.,Kuromitsu,S.,Hirose,T.,Yasuda,S.,Furuichi,K.,Okumura,K.: "Soluble human high-affinity receptor for IgE abrogates the IgE-mediated allergic reaction." Int.Immunol.5. 47-54 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sandford,A.,Shirakawa,T.,Moffat,M.,Daniels,S.,Ra,C.,et al.: "Localisation of atopy and the β subnit of high-affinity IgE receptor(FcεRI)on chromosome 11q." The Lancet. 341. 332-334 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohno,H.,Aoe,T.,Ra,C.,Yamamoto,T.,Saito,T.: "TCR isoform containing the Fc receptor γ chain exhibits structural and functional differences from isoform containing CD3ζ." Int.Immunol.5. 1403-1411 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yagi,S.,Yanagida,M.,Tanida,I.,Okumura,K.,Ra,C.,et al.: "High-level expression of the truncated α chain of FcεRI as a soluble form by baculovirus infected insect cells:Biochemical characterization of the recombinant product." Eur.J.Biochem.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yagi,S.,Suzuki,K.,Hasegawa,A.,Okumura,K.,Ra,C.: "Cloning of the cDNA for the deleted Syk kinase homologous to Zap-70 from human basophilic leukemia cell line(KU 812)." Biochem.Biophys.Res.Commu.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shirakawa,T.,Li,A.,Dubowitz,M.K.,Dekker,J.W.,Shaw,A.,Faux,J.A.,Ra,C.,et al.: "Variants of the β subunit of the high affinity IgE receptor and atopy." Nature.Genetics.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 富岡 玖夫・羅 智靖: "マスト細胞とアレルギー:Mast cell revisited" 医科学出版社, 244 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平野 俊夫編: "免疫のしくみと疾患" 羊土社, 166 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ra.C., Kuromitsu, S., Hirose, T., Yasuda, S., Furuichi, K., Okumura, K.: "Soluble human high-affinity receptor for IgE abrogates the IgE-mediated allergic reaction." Int.Immunol.5. 47-54 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sandford, A., Shirakawa, T., Moffat, M., Daniels, S., . Ra.C., et at.: "Localisation of atopy and the beta subunit of high-affinity IgE receptor (FcepsilonRI) on chromosome 11q." The Lancet. 341. 332-334 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohno, H., Aoe, T., Ra, C., Yamamoto, T., Saito, T.: "TCR isoform containing the Fc receptor gamma chain exhibits structural and functional differences from isoform containing CD3zeta." Int.Immunol.5. 1403-1411 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yagi, S., Yanagida, M., Tanida, I., Okumura, K., Ra, C., et al.: "High-level expression of the truncated alpha chain of FcepsilonRI as a soluble form by baculovirus infected insect cells : Biochemical characterization of the recombinant product." Eur.J.Biochem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yagi, S., Suzuki, K., Hasegawa, A., Okumura, K., Ra, C.: "Cloning of the cDNA for the deleted Syk kinase homologous to Zap-70 from human basophilic leukemia cell line(KU 812)." Biochem.Biophys.Res.Commu.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shirakawa, T., Li, A., Dubowitz, M.K, Dekker, J.W., Shaw, A., Faux, J.A., Ra, C., et al.: "Variants of the beta subunit of the high affinity IgE receptor and atopy." Nature.Genetics.(in press).

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

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Published: 1995-03-27  

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