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Analysis of the signal transducing mechanism which leads to the antigenspecific activation or cell death of the lymphocytes.

Research Project

Project/Area Number 06454221
Research Category

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

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionMedical Institute of Bioregulation

Principal Investigator

WATANABE Takeshi  Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 教授 (40028684)

Co-Investigator(Kenkyū-buntansha) KITAMURA Daisuke  Institute of Life Science, Tokyo Science University, Professor, 生命科学研究所, 教授 (70204914)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1995: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsGeNe-targeting / Signal transduction / Antigen-receptor / Tyrosin kinase / Lyn kinase / HS1 / Apoptosis / Autoimmune disease / シグナル伝達 / 非受容体型チロシンキナーゼ / HS1タンパク / Two-hybrid-system / チロシンリン酸化 / リンパ球分化 / 免疫異常症
Research Abstract

In the present study, we established two kinds of gene-targeting mice.one is Lyn^deficient mice and the other, HS1-deficient mice, by applying homologous recomdination. Upon stimulation of cell surface antigen receptors on B cells, two kinds of tyrosine kinases are activated. One is src family tyosine kinasses such as Lyn, Fyn, Lck, Blk and so on. The other is Syk/ZAP70 kinase. In Lyndeficient mice, we found that the responses of the B cells were very low to the stimulation by anti-IgM,CD40 ligand and LPS.In spite of the decreased numbers of mature B cells in the periphery, splenomegaly, lymphadenopathy, hyper IgM syndrome are evident and antoantibodies were produed in Lyn-knockout mice. The mice developed finally autoimmune glomerulonephritis. HS1-deficient mice did not show autoimmune disease but the proliferative responses of B cells and T cells induced by anti-IgM or anti CD3 were impaired. Apoptosis induced by crosslinking of the surface antigen receptors was also impaired.
These results clearly indicate that Lyn-HS1 pathway plays a crucial role in signal transduction pathway from antigen-receptor complex on lymphocyte.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] K. Sonoda, et al: "A novel tumor-associated antigen expressed on human uterine and ovarian carcinomas." Cancer. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J. Wang, et al: "Expression and function of Fas antigen on activated murine B cells" Eur. J. Immunol.26. 92-96 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H. Nishizumi, et, al: "Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice." Immunity. 3. 549-560 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Fukuda, et al: "Restoration of surface IgM-mediated apoptosis in an anti-IgM resistant variant of WEHI-231 lymphoma cells by HS1, a protein tyrosine kinase substrate." Proc. Natl. Acad. Sci. USA. 92. 7302-7306 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I. Taniuchi, et al: "Antigen-receptor induced clonal expansion and delection of lymphoma of the antigen receptor coupled tyrosine kinases." EMBO J.14(15). 3664-3678 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T. Okabe, et al: "cDNA cloning of a NGF1-B/nur77 related transcription factor from and apoptotic T cell line." J. Immunol.154. 3871-3879 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Sonoda, M.Nakashima and T.Watanabe: "A novel tumorassociated antigen expressed on human uterine and ovarian carcinomas." Cancer. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Wang, I.Taniuchi, Y.Maekawa, M.Howard, M.D.Cooper and T.Watanabe: "Expression and funciton of Fas antigen on activated murine B cells" Eur.J.Immunol. 26. 92-96 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Nishizumi, I.Taniuchi, Y.Yamanashi, D.Kitamura, S.Mori, T.Watanabe, T.Yamamoto: "Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice." Innunity. 3. 549-560 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Fukuda, D.Kitamura, I.Taniuchi, Y.Maekawa, L.E.Benhamou, P.Sarthou and T.Watanabe: "Restoration of surface IgM-mediated apoptosis in an anti-IgM resistane variant of WEHI-231 lymphoma cells by HS1, a protein tyrosine kinase substrate." Proc.Natl.Acad.Sci.USA. 92. 7302-7306 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Taniuchi, D.Kitamura, Y.Maekawa, H.Kishi and T.Watanabe: "Antigen-receptor induced clonal expansion and deletion of lymphocytes are impaired in the mice lacking HS1 protein, a substrate of the antigen-receptor coupled tyrosine kinases." EMBOJ. 14(15). 3664-3678 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Okabe, M.Haji, R.Takayanagi, M,Adachi, K.Imasaki, F.Kurimoto, T.Watanabe and H.Nawata: "Up-regulation of high affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in human T lymphocytes." Journal of Clinical Endocrinology and Metabolism. 80(10). 2993-2996 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K. Sonoda, et al: "A novel tumor-associated antigen expressed on human uterine and ovarian carcinomas." Cancer. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] J. Wang, et al: "Expression and function of Fas antigen on activated murine B cell" Eur. J. Immunol.26. 92-96 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] H. Nishizumi, et, al: "Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice." Immunity. 3. 549-560 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T. Fukuda, et al: "Restoration of surface IgM-mediated apoptosis in an anti-IgM resistant variant of WEHI-231 lymphoma cells by HS1, a protein tyrosine kinase substrate." Proc. Natl. Acad. Sci. USA. 92. 7302-7306 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] I. Taniuchi, et al: "Antigen-receptor induced clonal expansion and delection of lympho cytes are imbaired in the mice lacking HS1 protein, a substrate of the antigen receptor couled tyrosine kinases." EMBO J.14(15). 3664-3678 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T. Okabe, et al: "cDNA cloning of a NGF1-B/nur77 related transcription factor from and apoptotic T cell line." J. Immunol.154. 3871-3879 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Benhamou,L.E.: "Signaling properties of anti-immunoglobulin resistant variants of WEHI-231 B lymphoma cells." Eur.J.Immunology. 24. 1933-1999 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakashima,M.: "In vitro expansion of melanoma specific,HLA restricted CD8+cytotoxic T lymphocyts." Cellular Immunomol.155. 53-61 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ezaki,I.: "Analysis of the gene encoding the variable regions of a human IgG theumatoid factor." J.Rheumatology. 21. 2005-2010 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hara,H.: "Detection of human T lymphotropic Virus Type I (HTLV-I) proviral DNA and analysis of T cell receptor Vβ CDR3 sequences in spinal cord lesions of HTKV-I associated myelophathy/Tropical spastic paraparesis" J.Experimental Medicine. 180. 831-839 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kukita,T.: "A novel cell surface antigen expressed on rat osteoclast regulating the functio of the calcitonin receptor." J.Immunology. 153. 5265-5273 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sato,S.: "IL-5 receptor-mediated phosphorylation of SH2/SH3-containing proteins and activation of Btk and Jak2 kinases." J.Experimental Medicine. 180. 2101-21 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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