Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein
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Communicated by David V. Goeddel, Tularik, Inc., South San Francisco, CA (received for review July 29, 1997)
Abstract
The proinflammatory cytokine interleukin 1 (IL-1) activates the transcription of many genes encoding acute phase and proinflammatory proteins, a function mediated primarily by the transcription factor NF-κB. An early IL-1 signaling event is the recruitment of the Ser/Thr kinase IRAK to the type I IL-1 receptor (IL-1RI). Here we describe the function of a previously identified IL-1 receptor subunit designated IL-1 receptor accessory protein (IL-1RAcP). IL-1 treatment of cells induces the formation of a complex containing both IL-1RI and IL-1RAcP. IRAK is recruited to this complex through its association with IL-1RAcP. Overexpression of an IL-1RAcP mutant lacking its intracellular domain, the IRAK-binding domain, prevented the recruitment of IRAK to the receptor complex and blocked IL-1-induced NF-κB activation.
Footnotes
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↵ * To whom reprint requests should be addressed. e-mail: Cao{at}Tularik.com.
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Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF029213).
- ABBREVIATIONS:
- IL-1,
- interleukin 1;
- IL-1RI,
- type I IL-1 receptor;
- TNF,
- tumor necrosis factor;
- IL-1RAcP,
- IL-1 receptor accessory protein;
- EMSA,
- electrophoretic mobility-shift assay
- Copyright © 1997, The National Academy of Sciences of the USA
