The Fc epsilon RI beta subunit functions as an amplifier of Fc epsilon RI gamma-mediated cell activation signals

The high affinity IgE receptor (Fc epsilon RI) plays a central role in the initiation of allergic responses. Fc epsilon RI is multimeric and is expressed as either alpha gamma(2) trimers or alpha beta gamma(2) tetramers. Recently, polymorphisms of the beta chain gene have been associated with the development of various allergic phenotypes. Until now, the role of beta in Fc epsilon RI-dependent signaling was largely unknown. For that reason, we compared the signaling characteristics of various wild-type and mutant alpha gamma(2) and alpha beta gamma(2) Fc epsilon RI complexes. These studies demonstrate that the gamma dimer functions as an autonomous activation module, while beta functions as an amplifier that provides a gain of 5- to 7-fold, as measured by Syk activation and calcium mobilization.