The IL-4 Receptor α-Chain Cytoplasmic Domain Is Sufficient for Activation of JAK-1 and STAT6 and the Induction of IL-4-Specific Gene Expression

Martin Reichel, Brad H. Nelson, Philip D. Greenberg, Paul B. Rothman

Research output: Contribution to journalArticlepeer-review

Abstract

The common γ-chain (γc) is a functional component of the IL-4R, yet cells lacking γc are able to respond to IL-4. This has led to the suggestion that a surrogate γ′-chain, which can interact with the IL-4Rα chain to mediate signaling, is expressed on cells lacking γc. An alternative possibility is that in the absence of γc, the IL-4Rα chain is able to transduce signals by homodimerization. To test this latter possibility, a chimeric receptor containing the extracellular domain of c-kit (the stem cell factor (SCF) receptor) and the cytoplasmic and transmembrane domains of the IL-4Rα chain was generated. Treatment of cells expressing the chimeric receptor kit/IL-4Rα with SCF induces activation of the IL-4Rα-associated kinase JAK-1 and the transcription factor STAT6. However, tyrosine phosphorylation of JAK-3, which associates with γc, is not induced by SCF in these cells. SCF-mediated ligation of kit/IL-4Rα is sufficient to elicit IL-4-specific gene expression, including up-regulation of CD23 and synthesis of germ-line ∈ transcripts. In the T cell line CTLL2, ligation of kit/IL-4Rα induces cellular proliferation. Finally, in JAK-1-deficient HeLa cells, STAT6 activation by IL-4 is completely abolished. Together, these data demonstrate that the IL-4Rα cytoplasmic domain is sufficient to activate JAK-1 and STAT6 and to induce expression of IL-4 target genes, thus identifying a mechanism by which IL-4 signaling can proceed in the absence of JAK-3 and αc.

Original languageEnglish (US)
Pages (from-to)5860-5867
Number of pages8
JournalJournal of Immunology
Volume158
Issue number12
StatePublished - Jun 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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