title: Type I IL-4Rs selectively activate IRS-2 to induce target gene expression in macrophages.
abstract: Although interleukin-4 (IL-4) and IL-13 participate in allergic inflammation and share a receptor subunit (IL-4Ralpha), 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, gammaC-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, gammaC-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.
authors.affiliation: Center for Vascular and Inflammatory Diseases, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Heller
authors.forename: Xiulan
authors.initials: X
authors.lastname: Qi
authors.forename: Ilkka S
authors.initials: IS
authors.lastname: Junttila
authors.forename: Kari Ann
authors.initials: KA
authors.lastname: Shirey
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Vogel
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.forename: Achsah D
authors.initials: AD
authors.lastname: Keegan
mesh_terms: D002460:Cell Line; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D018793:Interleukin-13 / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D010766:Phosphorylation; D053658:Receptors, Interleukin-4, Type I / Q000502:physiology*; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D055504:Insulin Receptor Substrate Proteins; D018793:Interleukin-13; D053658:Receptors, Interleukin-4, Type I; D050800:STAT6 Transcription Factor