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. Interestingly, the RNA destabilizing protein tristetraprolin (TTP) was induced following IgE crosslinkage in Stat5KO but not wild type cells. Moreover, reducing TTP expression via shRNA transfection significantly increased IL‐13 production in Stat5KO mast 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. 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 grant 1R01 AI59638.
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