Progress in allergy signal research on mast cells: Signal regulation of multiple mast cell responses through FcεRI

The crosslinking of FcεRI by IgE and antigen (Ag) on mast cells initiates activation cascades that lead to allergic responses. Although it was thought that IgE binding to FcεRI is a passive "sensitization", recent reports suggest that IgE actively promotes mast cell survival in the absence of Ag. However, it is largely unknown how these distinct responses are delivered through the same receptor, FcεRI, depending on the types of stimli. As an underlying molecular mechanism for the generation of diverse responses through FcεRI, we found that the quantity and the duration of the signal through the FcεRI γ chain (FcRγ) determine different mast cell responses. Furthermore, FcRγ-mediated sustained Erk activation is critical for IgE-induced mast cell survival through autocrine production of IL-3. Transmembrane adaptors LAT and NTAL contribute to the maintenance of prolonged Erk activation through membrane retention of the Ras-activating complex, Grb2-Sos. In this review, the signal regulation for the distinct responses of mast cells through FcεRI are discussed.