An interleukin (IL)-13 receptor lacking the cytoplasmic domain fails to transduce IL-13-induced signals and inhibits responses to IL-4

Orchansky, PL; Ayres, SD; Hilton, DJ; Schrader, JW

Author(s): Orchansky, PL; Ayres, SD; Hilton, DJ; Schrader, JW;
Details: Publication Year 1997-09-05,Volume 272,Issue #36,Page 22940-22947
Journal Title: JOURNAL OF BIOLOGICAL CHEMISTRY
Publication Type: Journal Article
Abstract: Interleukin (IL)-13 is a pleiotropic immunoregulatory cytokine that shares many, although not all, of the biological activities of IL-4. The overlapping biological properties of IL-4 and IL-13 appear to be due to the existence of shared components of the receptors, and we and others showed that the IL-4 receptor-alpha is involved in signal transduction paths activated by both. We show here that expression of the IL-13 receptor-alpha in two factor-dependent cell lines, the premyeloid FD5 and the T lymphoid CT4.S, conferred the ability to grow continuously in response to IL-13; to respond to IL-13 with tyrosine phosphorylation of JAK1, Tyk2, IL-4R alpha, IRS-2, and STAT6; and to respond to IL-4 with tyrosine phosphorylation of Tyk2 in addition to those induced in parental cell lines. Expression of a truncated IL-13 receptor-alpha that lacked the cytoplasmic domain demonstrated that this domain was essential for IL-13-dependent growth and phosphorylation of the above substrates. Expression of this truncated IL-13 receptor also resulted in an inhibition of biochemical and biological responses to IL-4 that was exacerbated by the presence of IL-13. These dominant inhibitory effects indicate that the extracellular domain of the truncated IL-13 receptor competes with gamma c for complexes of IL-4 and the IL-4 receptor-alpha, or, when itself bound to IL-13, competes with IL-4 for the IL-4 receptor-alpha.
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Keywords: GAMMA-CHAIN; ALPHA-CHAIN; STIMULATING FACTOR; T-CELLS; HEMATOPOIETIC-CELLS; KINASE ACTIVATION; BINDING SUBUNIT; JANUS KINASE; BETA-SUBUNIT; B-CELLS
Publisher's Version: https://doi.org/10.1074/jbc.272.36.22940
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1997-09-05 12:00:00