Type I IL-4Rs selectively activate IRS-2 to induce target gene expression in macrophages

Nicola Mary Heller, Xiulan Qi, Ilkka S. Junttila, Kari Ann Shirey, Stefanie N. Vogel, William E. Paul, Achsah D. Keegan

Research output: Contribution to journalArticle

Abstract

Although interleukin-4 (IL-4) and IL-13 participate in allergic inflammation and share a receptor subunit (IL-4Rα), they have different functions. We compared cells expressing type I and II IL-4Rs with cells expressing only type II receptors for their responsiveness to these cytokines. IL-4 induced highly efficient, γC-dependent tyrosine phosphorylation of insulin receptor substrate 2 (IRS-2), whereas IL-13 was less effective, even when phosphorylation of signal transducer and activator of transcription 6 (STAT6) was maximal. Only type I receptor, γC-dependent signaling induced efficient association of IRS-2 with the p85 subunit of phosphoinositide 3-kinase or the adaptor protein growth factor receptor- bound protein 2. In addition, IL-4 signaling through type I IL-4Rs induced more robust expression of a subset of genes associated with alternatively activated macrophages than did IL-13. Thus, IL-4 activates signaling pathways through type I IL-4Rs qualitatively differently from IL-13, which cooperate to induce optimal gene expression.

Original languageEnglish (US)
JournalScience Signaling
Volume1
Issue number51
DOIs
StatePublished - Dec 23 2008
Externally publishedYes

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Insulin Receptor Substrate Proteins
Interleukin-13
Macrophages
Gene expression
Interleukin-4
Gene Expression
Phosphorylation
GRB2 Adaptor Protein
STAT6 Transcription Factor
Cells
1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
Tyrosine
Phosphotransferases
Genes
Association reactions
Cytokines
Inflammation
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Type I IL-4Rs selectively activate IRS-2 to induce target gene expression in macrophages. / Heller, Nicola Mary; Qi, Xiulan; Junttila, Ilkka S.; Shirey, Kari Ann; Vogel, Stefanie N.; Paul, William E.; Keegan, Achsah D.

In: Science Signaling, Vol. 1, No. 51, 23.12.2008.

Research output: Contribution to journalArticle

Heller, Nicola Mary ; Qi, Xiulan ; Junttila, Ilkka S. ; Shirey, Kari Ann ; Vogel, Stefanie N. ; Paul, William E. ; Keegan, Achsah D. / Type I IL-4Rs selectively activate IRS-2 to induce target gene expression in macrophages. In: Science Signaling. 2008 ; Vol. 1, No. 51.
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AU - Vogel, Stefanie N.

AU - Paul, William E.

AU - Keegan, Achsah D.

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