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- Title
Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor.
- Authors
Burns, Kimberly; Clatworthy, Jonathan; Martin, Laurence; Martinon, Fabio; Plumpton, Chris; Maschera, Barbara; Lewis, Alan; Ray, Keith; Tschopp, Jürg; Volpe, Filippo
- 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.
- Subjects
INTERLEUKIN-1; CYTOKINES; TRANSCRIPTION factors; SERINE
- Publication
Nature Cell Biology, 2000, Vol 2, Issue 6, p346
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/35014038