Article abstract
Nature Cell Biology 2, 346 - 351 (2000)
Published online: 10 May 2000 | doi:10.1038/35014038
Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor
Kimberly Burns1, Jonathan Clatworthy2,3, Laurence Martin1, Fabio Martinon1, Chris Plumpton2,4, Barbara Maschera2,3, Alan Lewis2,4, Keith Ray2,4, Jürg Tschopp1,5 & Filippo Volpe2,3,4,5
Abstract
Interleukin-1 (IL-1) is a proinflammatory cytokine that elicits its pleiotropic effects through activation of the transcription factors NF-
B 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-1
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-B activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway.
- Institute of Biochemistry, University of Lausanne, BIL Biomedical Research centre, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
- Glaxo Wellcome, Gunnels Wood Road, Stevenage SG1 2NY, UK
- Cell Biology, Gunnels Wood Road, Stevenage SG1 2NY, UK
- Molecular Pharmacology, Gunnels Wood Road, Stevenage SG1 2NY, UK
- These authors contributed equally to this work
Correspondence to: Jürg Tschopp1,5 e-mail: jurg.tschopp@ib.unil.ch
