IL-4/IL-13 signaling beyond JAK/STAT

Hong Jiang, Miera B. Harris, Paul Rothman

Research output: Contribution to journalArticle

Abstract

In the past several years, extensive studies on the mechanisms underlying IL-4 and IL-13 signaling have enabled us to gain insight into how these cytokines regulate immune responses. Because both IL-4 and IL-13 use the IL-4Ra as a receptor component, these cytokines activate many common signaling pathways. Both of these cytokines use Janus kinases (JAKs) to initiate signaling and activate signal transducer and activator of transcription-6 (STAT6), which is a transcription factor required for many of their biologic functions. In addition to JAK/STAT, these cytokines also activate a variety of other signaling molecules that are important in regulating IL-4-induced proliferation and protection from apoptosis. Suppressor of cytokine signaling-1 (SOCS-1) is a molecule that can inhibit the activation of IL-4 signaling through the inhibition of JAKs. The Fes ty rosine kinase is activated by IL-4 and appears to be important in regulating IL4-induced proliferation through the phosphorylation of insulin receptor substrate (1RS) molecules. 1RS molecules are essential for IL-4-induced proliferation through their ability to recruit phosphoinositol-3 kinase to the activated IL-4 receptor kinase. In addition, IL-4 can activate a number of phosphatases including SH2-containing inositol phosphatase (SHIP), SHP-1, and SHP-2. Finally, B-cell lymphoma gene-6 (BCL-6) appears to regulate a subset of IL-4-induced genes. Thus the biologic responses induced by IL-4/IL-13 require a complex interaction of signaling pathways and regulators,

Original languageEnglish (US)
Pages (from-to)1063-1070
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume105
Issue number6 II
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • BCL-6
  • Cell signaling
  • Dok
  • Fes
  • IL-13
  • IL-4
  • IRS
  • Interleukins
  • SOCS
  • Transcription factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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