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Dynamic regulation of Src-family tyrosine kinases by CD45

Research Project

Project/Area Number13680731
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

KATAGIRI Tatsuo  TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY, FACULTY OF PHARMACEUTICAL SCIENCES, ASSOCIATE PROFESSOR, 薬学部, 助教授 (00233742)

Co-Investigator(Kenkyū-buntansha) YAKURA Hidetaka  TOKYO METROPOLITAN INSTIRUTE FOR NEUROSCIENCE, DIRECTOR OF DEPARTMENT, 東京都神経科学総合研究所, 参事研究員 (60166486)
Project Period (FY) 2001 – 2002
Project Status Completed(Fiscal Year 2002)
Budget Amount *help
¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 2002 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 2001 : ¥1,800,000 (Direct Cost : ¥1,800,000)
KeywordsB cell reseptor signal / Lipid Raft / GEM / CD45 / PTP / PTK / Src-family PTK / Lyn
Research Abstract

Initiation of immune responses is determined by activation of Src-family protein tyrosine kinases (Src-PTKs) upon antigen receptor ligation. Activity of Src-PTKs is regulated, among others, by tyrosine phosphorylation of two tyrosine residues: the autophosphorylation and COOH-terminal negative regulatory sites. CD45, the prototypic receptor-type protein tyrosine phosphatase, has been shown to be a major regulator of Src-PTKs. The precise way in which CD45 exerts its effect is still controversial, however. Our earlier studies showed that CD45 inhibits Lyn activity in a B cell line by dephosphorylating both the autopfibsphorylation and negative regulatory tyrosine residues, and that B cell receptor (BCR) ligation induces phosphorylation of both regulatory sites, suggesting CD45 action on Lyn is diminished upon BCR ligation. In this presentation, we report that in contrast to most studies reported thus far, negative regulation by CD45 is generally operative in B cells, and that some CD45 is constitutively associated with glycolipid-enriched microdomains (GEMs), where it inhibits Src-PTK activity. Upon BCR ligation, however, CD45 dissociates from GEMs within 1 min, leading to activation of Src-PTKs, and then subsequently re-associates with the GEMs within 60 min. CD45 is not involved in the regulation of movement of IgM, Src-PTKs and Csk with respect to GEMs. We propose that the primary role of GEM-associated CD45 is inhibition of Src-PTKs, and that its dynamic behavior of CD45 determines the level of Src-PTK activation and the cell fate.

Report

(3results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(15results)

All Other

All Publications

  • [Publications] Ogimoto Mami: "Opposing regulation of B cell receptor-induced activation of mitogen-activated protein kinases by CD45"FEBS Letters. 490. 97-101 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arimura Yutaka: "CD45 is required for CD40-induced inhibition of DNA synthesis and regulation of c-Jun NH2-terminal kinase and p38 in BAL-17 B cells"The Journal of Biological Chemistry. 276. 8550-8556 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Adachi Takahiro: "SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates"The Journal of Biological Chemistry. 276. 26648-26655 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno Kazuya: "Src homology region 2 domain-containing phosphatase 1 positively regulates B cell receptor-induced apoptosis by modulating association of B cell linker protein with Nck and activation of c-Jun NH2-terminal kinase"The Journal of Immunology. 169. 778-786 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogimoto M., Arimura Y., Katagiri T., Mitomo K., Woodgett J.R., Nebreda A.R., Mizuno K. & Yakura H.: "Opposing regulation of B cell receptor-induced activation of mitogen-activated protein kinases by CD45"FEBS Lett. 490. 97-101 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arimura Y., Ogimoto M., Mitomo K., Katagiri T., Yamamoto K., Volarevic S., Mizuno K. & Yakura H.: "CD45 is required for CD40-induced inhibition of DNA synthesis and regulation of c-Jun NH2-terminal kinase and p38 in BAL-17 B cells"J Biol Chem. 276. 8550-8556 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Adachi T., Wienand J., Wakabayashi C., Yakura H., Reth M. & Tsubata T.: "SHP-1 requires inhibitory, co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates"J Biol Chem. 276. 26648-26655 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno K., Tagawa Y., Mitomo K., Watanabe N., Katagiri T., Ogimoto M. & Yakura H.: "Src homology region 2 domain-containing phosphatase 1 positively regulates B cell receptor-induced apoptosis by modulating association of B cell linker protein with Nck and activation of c-Jun NH2-terminal kinase."J Immunol. 169. 778-786 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arimura Yutaka: "CD45 is required for CD4O-induced inhibition of DNA synthesis and regulation of c-Jun NH2-terminal kinase and p38 in BAL-17 B cells"The Journal of Biological Chemistry. 276. 8550-8556 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Adachi Takahiro: "SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates"The Journal of Biological Chemistry. 276. 26648-26655 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogimoto Mami: "Opposing regulation of B cell receptor-induced activation of mitogen-activated protein kinases by CD45"FEBS Letters. 490. 97-101 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizuno Kazuya: "Src homology region 2 domain-containing phosphatase 1 positively regulates B cell receptor-induced apoptosis by modulating association of B cell linker protein with Nck and activation of c-Jun NH2-terminal kinase"The Journal of Immunology. 169. 778-786 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arimura Yutaka: "CD45 is required for CD40-induced inhibition of DNA synthesis and regulation of c-Jun NH2-terminal kinase and p38 in BAL-17B cells"The Journal of Biological Chemistry. 276号. 8550-8556 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Adachi Takahiro: "SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates"The Journal of Biological Chemistry. 276号. 26648-26655 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogimoto Mami: "Opposing regulation of B cell receptor-induced activation of mitogen-activated protein kinases by CD45"FEBS Letters. 490号. 97-101 (2001)

    • Related Report
      2001 Annual Research Report

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Published : 2001-04-01   Modified : 2016-04-21  

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