Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor
Author: ["Kimberly Burns","Jonathan Clatworthy","Laurence Martin","Fabio Martinon","Chris Plumpton","Barbara Maschera","Alan Lewis","Keith Ray","Jürg Tschopp","Filippo Volpe"]
Publication: Nature Cell Biology
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Abstract
Interleukin-1 (IL-1) is a proinflammatory cytokine that elicits its pleiotropic effects through activation of the transcription factors NF-κB and AP-1. Binding of IL-1 to its receptor results in rapid assembly of a membrane-proximal signalling complex that consists of two different receptor chains (IL-1Rs), IL-1RI and IL-1RAcP, the adaptor protein MyD88, the serine/threonine kinase IRAK and a new protein, which we have named Tollip. Here we show that, before IL-1β treatment, Tollip is present in a complex with IRAK, and that recruitment of Tollip–IRAK complexes to the activated receptor complex occurs through association of Tollip with IL-1RAcP. Co-recruited MyD88 then triggers IRAK autophosphorylation, which in turn leads to rapid dissociation of IRAK from Tollip (and IL-1Rs). As overexpression of Tollip results in impaired NF-κB activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway.
Cite this article
Burns, K., Clatworthy, J., Martin, L. et al. Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat Cell Biol 2, 346–351 (2000). https://doi.org/10.1038/35014038
