Analysis of the life cycle of Stat6. Continuous cycling of Stat6 is required for IL-4 signaling

Ryan P. Andrews, Mark B. Ericksen, Christie M. Cunningham, Michael O. Daines, Gurjit K. Khurana Hershey

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Signal transducer and activator of transcription (Stat)6 is a transcription factor important for the development of Th2 cells and regulation of gene expression by IL-4 and IL-13. It is known that Stat6 is rapidly activated in response to IL-4; however, the fate of activated Stat6 is less clear. We examined the fate of activated Stat6 and found that during continuous exposure to IL-4, Stat6 activity was sustained for 72 h and that the maintenance of a constant level of activated Stat6 did not require new protein synthesis. In contrast, when cells were pulsed with IL-4 and then incubated in the absence of IL-4, the half-life of Stat6 phosphorylation and DNA binding activity was less than 1 h. Stat6 did not accumulate in the nucleus, and protein degradation did not play a major role in the disappearance of activated Stat6. Inhibition of kinase activity by staurosporine or the JAK inhibitor, AG490, revealed that maintenance of Stat6 activation in the continuous presence of IL-4 required ongoing phosphorylation of latent cytoplasmic Stat6 molecules. Cells treated with an inhibitor of nuclear export, leptomycin B, were unable to maintain Stat6 activation. Thus, the maintenance of Stat6 activation requires a constant cycle of activation, deactivation, nuclear export, and reactivation.

Original languageEnglish (US)
Pages (from-to)36563-36569
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number39
DOIs
StatePublished - Sep 27 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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