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Sci. Signal., 23 December 2008
Vol. 1, Issue 51, p. ra17
[DOI: 10.1126/scisignal.1164795]

RESEARCH ARTICLES

Type I IL-4Rs Selectively Activate IRS-2 to Induce Target Gene Expression in Macrophages

Nicola M. Heller1,2, Xiulan Qi1,2, Ilkka S. Junttila3, Kari Ann Shirey2, Stefanie N. Vogel2, William E. Paul3, and Achsah D. Keegan1,2*

1 Center for Vascular and Inflammatory Diseases, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
2 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
3 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract: Although interleukin-4 (IL-4) and IL-13 participate in allergic inflammation and share a receptor subunit (IL-4R{alpha}), 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, {gamma}C-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, {gamma}C-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.

* To whom correspondence should be addressed. E-mail: akeegan{at}som.umaryland.edu

Citation: N. M. Heller, X. Qi, I. S. Junttila, K. A. Shirey, S. N. Vogel, W. E. Paul, A. D. Keegan, Type I IL-4Rs Selectively Activate IRS-2 to Induce Target Gene Expression in Macrophages. Sci. Signal. 1, ra17 (2008).

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