New programming of IL-4 receptor signal transduction in activated T cells: Stat6 induction and Th2 differentiation mediated by IL-4Rα lacking cytoplasmic tyrosines

Ana L. Mora, Linda M. Stephenson, Ben Enerson, Jeehee Youn, Achsah D. Keegan, Mark Boothby

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Signaling by the IL-4 receptor α-chain (IL-4Rα) is a key determinant of the development of the Th2 lineage of effector T cells. Studies performed in tissue culture cell lines have indicated that tyrosines of the IL-4Rα cytoplasmic tail are necessary for the induction of Stat6, a transcription factor required for Th2 differentiation. Surprisingly, we have found that in activated T cells, IL-4Rα chains lacking all cytoplasmic tyrosines promote induction of this IL-4-specific transcription factor and efficient commitment to the Th2 lineage. Mutagenesis of a tyrosine-free cytoplasmic tail identifies a requirement for the serine-rich ID-1 region in this new program of IL-4R signal transduction observed in activated T cells. Additional findings suggest that an extracellular signal-regulated kinase pathway can be necessary and sufficient for the ability of such tyrosine-free IL-4Rα chains to mediate Stat6 induction. These results provide novel evidence that the molecular mechanisms by which a cytokine specifically induces a Stat transcription factor can depend on the activation state of T lymphoid cells. Furthermore, the data suggest that one pathway by which such new programming may be achieved is mediated by extracellular signal-regulated mitogen-activated protein kinases.

Original languageEnglish
Pages (from-to)1891-1900
Number of pages10
JournalJournal of Immunology
Volume171
Issue number4
StatePublished - 2003 Aug 15

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