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

• Published in: The Journal of biological chemistry 1995-07, Vol.270 (30), p.17645-17648
• Main Authors: Reikerstorfer, A, Holz, H, Stunnenberg, H G, Busslinger, M
• Format: Article
• Language: English
• Subjects: Base Sequence; Interleukin-1 - metabolism; Interleukin-1 Receptor-Like 1 Protein; Membrane Proteins; Molecular Sequence Data; NF-kappa B - metabolism; Oligodeoxyribonucleotides; Protein Binding; Proteins - genetics; Proteins - isolation & purification; Proteins - metabolism; Receptors, Interleukin; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - isolation & purification; Receptors, Interleukin-1 - metabolism; Signal Transduction
• ISSN: 0021-9258
• DOI: 10.1074/jbc.270.30.17645

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.