マスト細胞依存的なアレルギー応答におけるアダプター分子Gab2の役割  [in Japanese] Role of Adaptor Molecule Gab2 in Mast Cell-mediated Allergy Response  [in Japanese]

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Author(s)

    • 西田 圭吾 Nishida Keigo
    • 独立行政法人理化学研究所免疫・アレルギー科学総合研究センターサイトカイン制御研究グループ Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology

Abstract

  Mast cells are major players in allergic responses. IgE-dependent activation through Fc epsilon RI leads to degranulation and cytokine production, both of which require Gab2. To clarify how the signals diverge at Gab2, we established Gab2 knock-in mice that express Gab2 mutated at either the PI-3K- or SHP-2-binding sites. Examination of these mutants showed that both binding sites were required for the degranulation and anaphylaxis response, but not for cytokine production or contact hypersensitivity. Furthermore, the PI-3K- but not the SHP-2-binding site was important for granule translocation during degranulation. We also identified a small GTPase, ARF1, as the downstream target of PI-3K that regulates granule translocation. Fc epsilon RI-stimulation induced ARF1 activation, and this response was dependent on Fyn and the PI-3K-binding site of Gab2. ARF1 activity was required for the Fc epsilon RI-mediated granule translocation. These results indicate that Fyn/Gab2/PI-3K/ARF1-mediated signaling is specifically involved in granule translocation and the anaphylaxis response. In this review, I discussed how Gab2 controls biological events especially for mast cell degranulation and allergy response.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 133(4), 413-418, 2013

    The Pharmaceutical Society of Japan

Cited by:  1

Codes

  • NII Article ID (NAID)
    130003361932
  • NII NACSIS-CAT ID (NCID)
    AN00284903
  • Text Lang
    JPN
  • Article Type
    Journal Article
  • ISSN
    0031-6903
  • NDL Article ID
    024608389
  • NDL Call No.
    Z19-411
  • Data Source
    CJPref  NDL  J-STAGE 
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