Abstract
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.
Highlights
From the :j:Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria and the §European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69012 Heidelberg, Germany
The fit-1 gene gives rise to two different mRNA isoforms, which code for soluble (Fit-lS) and membranebound (Fit-1M) proteins related to the type I interleukin (IL)-1 receptor
Purification of Fit-IS and s!L-IR- IL-1 binding studies are usually performed with membra ne-bound IL-l receptors present on intact cells
Summary
A chimeric protein consisting of the extracellular domain of the type I IL-l receptor and of the transmembrane and intracellular regions of Fit-1M stimulated NF-KB-dependent transcription as efficiently as the full-length type I IL-l receptor. These data indicate that Fit-1M is a signaling molecule belonging to the IL-l receptor family. The extracellular domains ofFit-1 and the two IL-l receptors (type I and II) share a similar degree of amino acid sequence identity (26-29%), suggesting that the Fit-1 proteins may bind IL-l. We demonstrate that Fit-1 is a distant member of the IL-l receptor family based on its IL-l{:l binding and intracellular signaling capacities
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