title: [Role of adaptor molecule Gab2 in mast cell-mediated allergy response].
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.
authors.affiliation: Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Nishida
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D015550:Cell Degranulation; D055879:Gene Knock-In Techniques; D006967:Hypersensitivity / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D015398:Signal Transduction / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human