IgE-receptor activation of mast cells regulates phosphorylation and expression of forkhead and bcl-2 family members

Activation of the high-affinity IgE-receptor, Fc epsilon RI, expressed on mast cells can result in either enhanced survival or apoptosis depending on the circumstances. In this study, we have analysed signalling pathways involved in the regulation of mast cell survival and apoptosis. Fc epsilon RI cross-linking induces phosphorylation of Akt and its downstream target forkhead transcription factors. In addition, Bad, GSK-3 beta and I kappa B-alpha also become phosphorylated. A1, a prosurvival Bcl-2 homologue transcriptionally controlled by NF kappa B transcription factors, is upregulated upon Fc epsilon RI activation. These events have prosurvival effects on the mast cells. Moreover, Fc epsilon RI activation upregulates the levels of the proapoptotic protein Bim and induces a rapid, but transient, phosphorylation of Bim. Thus, Fc epsilon RI activation of mast cells leads to both prosurvival and proapoptotic signalling events where the outcome most likely depends on the balance between these signals.