Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein.
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-kappaB. 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-kappaB activation.
Huang
J
J
Tularik, Inc., South San Francisco, CA 94080, USA.
Gao
X
X
Li
S
S
Cao
Z
Z
D000818:Animals; D018076:DNA, Complementary; D006367:HeLa Cells; D006801:Humans; D053577:Interleukin-1 Receptor Accessory Protein; D053592:Interleukin-1 Receptor-Associated Kinases; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011233:Precipitin Tests; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015398:Signal Transduction
D018076:DNA, Complementary; C507765:IL1RAP protein, human; C507767:Il1rap protein, mouse; D053577:Interleukin-1 Receptor Accessory Protein; D016328:NF-kappa B; D011506:Proteins; D017472:Receptors, Interleukin-1; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases