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Receptor-type Protein Tyroshine Phosphatases Expressed in the Immune System and the Central Nervous System

Research Project

Project/Area Number 04670299
Research Category

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

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionTOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCES

Principal Investigator

YAKURA Hidetaka  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology and Immunology, Director, 微生物学・免疫学研究部門, 副参事研究員 (60166486)

Co-Investigator(Kenkyū-buntansha) KATAGIRI Tatsuo  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学, 主任研究員 (00233742)
OGIMOTO Mami  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学, 主任研究員 (80158609)
MIZUNO Kazuya  Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology & Immu, 微生物学・免疫学, 主任研究員 (00219643)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsTyrosine phosphatase / CD45 / B cell / Central nervous system / signal transduction / MPTP-delta / Apoptosis / MPTPdelta / HPTPdelta / レセプター型チロシンフォスファターゼ / B細胞活性化 / MRPTP / HPTP / アイソフォーム・スイッチ
Research Abstract

Cell activation, proliferation, and differentiation are regulated by protein tyrosine phosphorylation. This process is strictly controlled by interplays between protein tyrosine kinases (PTKs) and protein tyrosin phosphatases (PTPs). In this project, we tried to resolve the mechanisms underlying the B cell activation and inactivation by analyzing the function of CD45, a prototypic PTP, and to gain some insights into the regulation of the central nervous system by identifying PTPgenes expressed in the brain. The followings are the results obtained from the studies of the last two years :
1. Differential regulation of B cell activation and inactivation by CD45
CD45-negative clones were established from an immature B cell line and a mature B cell line, and the functional properties of the CDE45-negative clones were compared with the parental cells. The results demonstrated that CD45 on immarture B cells negatively regulates antigen receptor-mediated signaling whereas in mature B cells, CD45 an indispensable positive regulatory molecule.
2. Regulation of CD45 PTP activity by the extracdellular domain
Changes in the PTP activity after binding of native CD45 with various CD45 monoclonal antibodies were measured. In the event, only one monoclonal antibody aginst a common epitope down-regulated the PTP activity, suggesting that the CD45 PTP activity is regulated by structural perturbations in specific regions of the extracellular domain.
3. Identification of PTPs expressed in the immune and the central nervous sytems
We isolated MPTP delta gene from mouse brain cDNA library. The cytoplasmic domain contained two tandem repeats of PTP domain and the extracellular domain was composed of Ig-like and fibronectin type III-like domains. MPTP delta mRNA was expressed in specialized regions of the brain and lymphoid cells. Futher, its expression was developmentally controlled both in the brain and in thymus.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] 水野一也: "中枢神経系および免疫系に発現するチロシンホスファターゼ" Medical Immunology. 25. 451-464 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizuno,Kazuya: "MPTPδ,a putative murine homolog of HPTPδ,is expressed in specialized regions of the brain and in the B-cell lineage." Mol.Cell.Biol.13. 5513-5523 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ogimoto,Mami: "CD45 isoform switch in murine mature B cells by antigen receptor stimulation and by PMA and ionomycin." Cell.Immunol.151. 97-109 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hasegawa,Kiminori: "Chromosomal assignment of the gene for protein tyrosine phophatase HPTPδ." Jpn.J.Cancer Res.84. 1219-1222 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ogimoto,Mami: "Negative regulation of apoptotic death in immature B cells by CD45." Int.Immunol.6(発表予定). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 矢倉英隆: "CD45とT,B細胞の機能分化" Medical Immunology. 26(発表予定). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ogimoto, M.: "Negative regulation of apoptotic death in immature B cells by CD45" Int. Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yakura, H.: "The role for protein tyrosine phosphatases in lymphocyte activation and differentiation" Crit. Rev. Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hasegarwa, K.: "Chromosomal assignment of the gene for protein tyrosine phosphatase HPTP delta" Jpn. J.Cancer Res.84. 1219-1222 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ogimoto, M.: "Induction of CD45 isoform switch in murine B cells by antigen receptor stimulation and by phorbol myristate acetate and ionomycin" Cell. Immunol.151. 97-109 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Misuno, K.: "MPTP delta, a putative murine homolog of HPTP delta, is expressed in specialized regions of the brain and in the B-cell lineage" Mol. Ccell. Biol.13. 5513-5523 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ogimoto, M.: "Regulation of lipopolysccharide- and IL-4-induced immunoglobilin heavy chain gene activation : differential roles for CD45 and Lyb-2" Int. Immunol.4. 651-659 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 水野一也: "中枢神経系および免疫系に発現するチロシンホスファターゼ" Medical Immunology. 25. 451-464 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mizuno,Kazuya: "MPTPdelta,a putative murine homolog of HPTPdelta,is expressed in specialized regions of the brain and in the B-cell lineage." Mol.Cell.Biol. 13. 5513-5523 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogimoto,Mami: "CD45 isoform switch in murine mature B cells by antigen receptor stimulation and by PMA and isnomycin." Cell.Immunol.151. 97-109 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hasegawa,Kiminori: "Chromosomal assignment of the gene for protein tyrosine phosphatase HPTPdelta." Jpn.J.Cancer Res.84. 1219-1222 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogimoto,Mami: "Negative vegulation of apoptotic death in immature B cell by CD45." Int.Immunol.6,発表予定. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 矢倉英隆: "CD45とT,B細胞の機能分化" Medical Immunology. 26,発表予定. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogimoto,Mami: "Regulation of lipopolysaccharide- and IL-4-induced immunoglobulin heavy chain gene activation:differential roles for CD45 and Lyb-2" International Immunology. 4. 651-659 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 荻本 真美: "免疫ブロブリン遺伝子再構成におけるCD45とLyb-2の役割" 臨床免疫.

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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