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

被引:134
作者
Heller, Nicola M. [1 ,2 ]
Qi, Xiulan [1 ,2 ]
Junttila, Ilkka S. [3 ]
Shirey, Kari Ann [2 ]
Vogel, Stefanie N. [2 ]
Paul, William E. [3 ]
Keegan, Achsah D. [1 ,2 ]
机构
[1] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA
[3] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1126/scisignal.1164795
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:14
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