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2005 Fiscal Year Final Research Report Summary

Regulation of mast Cell activation by tyrosine phosphatase

Research Project

Project/Area Number 16616010
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field アレルギー
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

YAKURA Hidetaka  Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Division of Neuronal Cell Function, Director, 東京都神経科学総合研究所, 参事研究員 (60166486)

Project Period (FY) 2004 – 2005
Keywordsallergy, asthma / signal transudation / immunology / enzyme / protein
Research Abstract

Antigen-induced ligation of the high affinity IgE receptor (FcεRI) on mast cells triggers a cascade of signaling events that ultimately lead to a wide variety of effector functions: release of granules, production of leukotrienes and prostaglandins, and secretion of cytokines and chemokines. To better understand the regulatory mechanisms of FcεRI-mediated signaling, we examined the role of two protein tyrosine phosphatases (PTPs), PTPε and PTP-PEST, that turned out to be induced upon FcεRI aggregation.
PTPε is a ubiquitously expressed PTP with two PTP domains. There are at least four isoforms generated from one gene : the transmembrane and three cytoplasmic isoforms. We found that bone marrow-derived mast cells from PTPε-deficient mice exhibited enhancement of FcεRI-induced Ca^<2+> mobilization, MAP kinase activation, leading to greater degranulation and cytokine responses. Furthermore, in vivo degranulation induced by IgE and antigen was also elevated in PTPε-deficient mice as assessed by passive systemic anaphylactic reaction. Thus PTPε may serve as a novel negative regulator in FcεRI-mediated mast cell activation (manuscript in preparation).
PTP-PEST, on the other hand, although introduction of substrate-trapping form of PTP-PEST (PTP-PEST-DACS) into RBL-2H3 cells did not affect initial signaling events, it did reduce phosphorylation of phospholipase C-γ and Ca^<2+> mobilization, inhibiting TNF-α expression without affecting degranulation. FcεRI-mediated activation of mitogen-activated protein kinases was also modulated in PTP-PEST-DACS-transfected cells. Significantly, in PTP-PEST-DACS transfectants, phosphoproteins (pp) of 65 kDa and 110 kDa were recruited to PTP-PEST upon FcεRI aggregation. These results suggest that PTP-PEST serve as a novel regulator of distinct aspects of FcεRI-mediated mast cell activation, possibly through actions of pp65 and pp110. We are now in the process of identifying these two phosphoproteins (manuscript in preparation).

  • Research Products

    (8 results)

All 2005 2004 Other

All Journal Article (8 results)

  • [Journal Article] チロシンホスファターゼによる免疫系の制御2005

    • Author(s)
      水野一也
    • Journal Title

      生化学 77

      Pages: 1281-1290

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] PEP(PEST domain-enriched tyrosine phosphatase)/LYP(Lymphoid tyrosine phosphatase)2005

    • Author(s)
      矢倉 英隆
    • Journal Title

      生化学 77

      Pages: 1340

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] SLP-76 is recruited to CD22 and dephosphorilated by SHP-1, thereby regulating B cell receptor-induced c-Jun N-terminal kinase activation2005

    • Author(s)
      Mizuno K
    • Journal Title

      Eur. J. Immunol 35

      Pages: 644-654

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Impairment of B cell receptor-mediated Ca^<2+> inglux, ativation of mitogen-activated protein kinases and growth inhibition in CD72-deficient BAL-17 cells2004

    • Author(s)
      Ogimoto M
    • Journal Title

      Int. Immunol 16

      Pages: 971-982

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Dynamic regulation of Src-family kinases by CD45 in B cells2004

    • Author(s)
      Shrivastava P^*, Katagiri T^*(^*equal contributors)
    • Journal Title

      Blood 103

      Pages: 1425-1432

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] SLP-76 is recruited to CD22 and dephosphorylated by SHP-1, thereby regulating B cell receptor-induced c-Jun N-terminal kinase activation

    • Author(s)
      Mizuno K, Tagawa Y, Watanabe N, Ogimoto M, Yakura H
    • Journal Title

      Eur.J.Immunol. 35

      Pages: 644-654

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Impairment of B cell receptor-mediated Ca^<2+> influx, activation of mitogen-activated protein kinases and growth inhibition in CD72-deficient BAL-17 cells

    • Author(s)
      Ogimoto M, Ichinowatari G, Watanabe N, Tada N, Mizuno K, Yakura H
    • Journal Title

      Int.Immunol. 16

      Pages: 971-982

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dynamic regulation of Src-family kinases by CD45 in B cells (*equal contributors)

    • Author(s)
      Shrivastava P*, Katagiri T*, Ogimoto M, Mizuno K, Yakura H
    • Journal Title

      Blood 103

      Pages: 1425-1432

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

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Published: 2007-12-13  

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