IgE Receptor Activates Stat5 via a Fyn-kinase Pathway (139.10)

Abstract We have recently found that the transcription factor Stat5 is rapidly activated by IgE crosslinkage, and that its expression is critical to IgE-mediated degranulation, LTB4 production, cytokine secretion, and survival signals. Stat5KO mast cells induced cytokine mRNAs normally following IgE crosslinkage, but these mRNAs were not sustained over time, and were degraded at twice the rate observed in wild type cells. We find that Stat5 is associated with the IgE receptor after antigen-mediated activation. Moreover, cholesterol depletion or Fyn kinase deletion prevents Stat5 tyrosine phosphorylation in response to IgE crosslinkage. In contrast, the Lyn, Syk, MAPK, and PI-3 kinase pathways do not appear to regulate Stat5 tyrosine phosphorylation via the IgE receptor. We also find that Stat5 is serine phosphorylated during IgE signaling. These data suggest that Stat5 is activated through a lipid raft- and Fyn-dependent pathway. Our work demonstrates that Stat5 is a critical factor in IgE-induced mast cell activation that could provide a new clinical target for mast cell-associated inflammatory diseases. Supported by NIH grants 1R01 AI59638 and U19A1077435.