Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor

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作者：

K Burns，J Clatworthy，L Martin，F Martinon，F Volpe

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摘要：

Interleukin-1 (IL-1) is a proinflammatory cytokine that elicits its pleiotropic effects through activation of the transcription factors NF-kappaB 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-1beta 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-kappaB activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway.

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关键词：

Cell Line Animals Humans Protein Kinases Mitogen-Activated Protein Kinases JNK Mitogen-Activated Protein Kinases Intracellular Signaling Peptides and Proteins Adaptor Proteins, Signal Transducing Carrier Proteins NF-kappa B