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Interleukin‐4‐specific signal transduction events are driven by homotypic interactions of the interleukin‐4 receptor alpha subunit.
Author(s) -
Lai S. Y.,
Molden J.,
Liu K. D.,
Puck J. M.,
White M. D.,
Goldsmith M. A.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00828.x
Subject(s) - library science , biology , humanities , philosophy , computer science
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.