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

Mora AL, Stephenson LM, Enerson B, Youn J, Keegan AD, Boothby M
J Immunol. 2003 171 (4): 1891-900

PMID: 12902491 · DOI:10.4049/jimmunol.171.4.1891

Signaling by the IL-4 receptor alpha-chain (IL-4Ralpha) 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-4Ralpha 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-4Ralpha 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-4Ralpha 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.

MeSH Terms (21)

Animals Cell Differentiation Cytoplasm Humans Jurkat Cells Lymphocyte Activation MAP Kinase Signaling System Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Mutagenesis, Site-Directed Peptide Fragments Protein Structure, Tertiary Protein Subunits Receptors, Interleukin-4 STAT6 Transcription Factor Th2 Cells Trans-Activators Tyrosine

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