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 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-4Ralpha, 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 gammac 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.
Orchansky
P L
PL
The Biomedical Research Centre, 2222 Health Sciences Mall, University of British Columbia, Vancouver V6T 1Z3, Canada. patricia@brc.ubc.ca
Ayres
S D
SD
Hilton
D J
DJ
Schrader
J W
JW
D000818:Animals; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D051379:Mice; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D015847:Interleukin-4; D014443:Tyrosine; D011494:Protein Kinases