AN INTERLEUKIN (IL)-13 RECEPTOR LACKING THE CYTOPLASMIC DOMAIN FAILS TO TRANSDUCE IL-13-INDUCED SIGNALS AND INHIBITS RESPONSES TO IL-4

Interleukin (IL)-13 is a pleiotropic immunoregulatory cytokine that sh ares 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 oth ers showed that the IL-4 receptor-alpha is involved in signal transduc tion paths activated by both. We show here that expression of the IL-1 3 receptor-alpha in two factor-dependent cell lines, the premyeloid FD 5 and the T lymphoid CT4.S, conferred the ability to grow continuously in response to IL-13; to respond to IL-13 with tyrosine phosphorylati on 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 i n parental cell lines. Expression of a truncated IL-13 receptor-alpha that lacked the cytoplasmic domain demonstrated that this domain was e ssential for IL-13-dependent growth and phosphorylation of the above s ubstrates. Expression of this truncated IL-13 receptor also resulted i n an inhibition of biochemical and biological responses to IL-4 that w as exacerbated by the presence of IL-13. These dominant inhibitory eff ects indicate that the extracellular domain of the truncated IL-13 rec eptor competes with gamma c for complexes of IL-4 and the IL-4 recepto r-alpha, or, when itself bound to IL-13, competes with IL-4 for the IL -4 receptor-alpha.