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. 1996 Sep 2;15(17):4506–4514.

Interleukin-4-specific signal transduction events are driven by homotypic interactions of the interleukin-4 receptor alpha subunit.

S Y Lai 1, J Molden 1, K D Liu 1, J M Puck 1, M D White 1, M A Goldsmith 1
PMCID: PMC452180  PMID: 8887542

Abstract

Interleukin-4 (IL-4) exerts its effects through a heterodimeric receptor complex (IL-4R), which contains the IL-4R(alpha) and gamma(c) subunits. IL-4R(alpha) also functions with other partner subunits in several receptor types, including the IL-13 receptor. To examine the roles of the individual subunits within IL-4R complexes, we employed a chimeric system that recapitulates native IL-4R function as verified by the activation of the kinases, JAK1 and JAK3, and induction of STAT-6. When a mutant gamma(c) subunit in which the four cytoplasmic tyrosines were converted to phenylalanine was paired with the cytoplasmic domain of the IL-4R(alpha) chain, specificity within the JAK-STAT pathway was not altered. Signaling events were examined further in cells expressing the IL-4R(alpha) chimera alone without the gamma(c) chimera. Ligand-induced homodimerization of these receptors activated the IL-4 signaling program despite the absence of gamma(c), including induction of JAK1 and STAT-6, phosphorylation of the insulin-related substrate 1 and cellular proliferation. Thus, homotypic interactions of the IL-4R(alpha) subunit are sufficient for the initiation and determination of IL-4-specific signaling events, and such interactions may be integral to signaling through IL-4R complexes.

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Selected References

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