The Adapter Molecule Gab2 Regulates FcεRI-Mediated Signal Transduction in Mast Cells

The Adapter Molecule Gab2 Regulates Fc RI-Mediated Signal Transduction in Mast Cells

Gab2, via PI-3K, regulates ARF1 in FcεRI-mediated granule translocation and mast cell degranulation.

Mast cells are major players in allergic responses. IgE-dependent activation through FcεR 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 PI3K or SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) binding sites. Examination of these mutants s...

Rcan1 negatively regulates FcεRI-mediated signaling and mast cell function

Aggregation of the high affinity IgE receptor (Fc epsilonRI) activates a cascade of signaling events leading to mast cell activation. Subsequently, inhibitory signals are engaged for turning off activating signals. We identified that regulator of calcineurin (Rcan) 1 serves as a negative regulator for turning off Fc epsilonRI-mediated mast cell activation. Fc epsilonRI-induced Rcan1 expression ...

Tespa1 negatively regulates FcεRI-mediated signaling and the mast cell–mediated allergic response

Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in their degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. We show that the activation of mast cells is negatively regulated by the newly identified adaptor protein Tespa1. Loss of Tespa1 in mouse mast cells led to hyper-responsiveness to stimulation ...

Mast Cells Produce Interleukin-25 upon FcεRI-mediated Activation

Interleukin (IL)-25 is a recently described T helper 2 (Th2) cell-derived cytokine that belongs to IL-17 family and induces the production of IL-4, IL-5, and IL-13 from an unidentified non-T cell population. Here, we show that mast cells are also potent IL-25-producing cells. When bone marrow-derived mast cells (BMMCs) were stimulated by IgE cross-linking, IL-25 mRNA was induced within 30 min i...