Low affinity binding of interleukin-1 beta and intracellular signaling via NF-kappa B identify Fit-1 as a distant member of the interleukin-1 receptor family.
The fit-1 gene gives rise to two different mRNA isoforms, which code for soluble (Fit-1S) and membrane-bound (Fit-1M) proteins related to the type I interleukin (IL)-1 receptor. To investigate IL-1 binding, we have synthesized and purified histidine-tagged polypeptides corresponding to Fit-1S and the extracellular domain of the type I IL-1 receptor using a vaccinia expression system. Fit-1S is shown to interact with IL-1 beta, but not with IL-1 alpha. However, Fit-1S binds IL-1 beta only with low affinity in contrast to the IL-1 receptor, suggesting that IL-1 beta is not a physiological ligand of Fit-1S. Moreover, expression of the membrane-bound protein Fit-1M in transiently transfected Jurkat cells did not result in activation of the transcription factor NF-kappa B following IL-1 beta treatment. However, a chimeric protein consisting of the extracellular domain of the type I IL-1 receptor and of the transmembrane and intracellular regions of Fit-1M stimulated NF-kappa B-dependent transcription as efficiently as the full-length type I IL-1 receptor. These data indicate that Fit-1M is a signaling molecule belonging to the IL-1 receptor family.
Reikerstorfer
A
A
Research Institute of Molecular Pathology, Vienna, Austria.
Holz
H
H
Stunnenberg
H G
HG
Busslinger
M
M
D001483:Base Sequence; D007375:Interleukin-1 / Q000378:metabolism*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D011485:Protein Binding; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1 / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D015398:Signal Transduction
C486189:Il1rl1 protein, mouse; D007375:Interleukin-1; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1