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 f or soluble (Fit-1S) and membrane-bound (Fit-1M) proteins related to th e type I interleukin (IL)-1 receptor. To investigate IL-1 binding, we have synthesized and purified histidine-tagged polypeptides correspond ing 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 on ly with low affinity in contrast to the IL-1 receptor, suggesting that IL-1 beta is not a physiological ligand of Fit-1S. Moreover, expressi on of the membrane-bound protein Fit-1M in transiently transfected Jur kat cells did not result in activation of the transcription factor NF- kappa B following IL-1 beta treatment. However, a chimeric protein con sisting of the extracellular domain of the type I IL-1 receptor and of the transmembrane and intracellular regions of Fit-1M stimulated NF-k appa B-dependent transcription as efficiently as the full-length type I IL-1 receptor. These data indicate that Fit-1M is a signaling molecu le belonging to the IL-1 receptor family.