MyD88: an adapter that recruits IRAK to the IL-1 receptor complex.
IL-1 is a proinflammatory cytokine that signals through a receptor complex of two different transmembrane chains to generate multiple cellular responses, including activation of the transcription factor NF-kappaB. Here we show that MyD88, a previously described protein of unknown function, is recruited to the IL-1 receptor complex following IL-1 stimulation. MyD88 binds to both IRAK (IL-1 receptor-associated kinase) and the heterocomplex (the signaling complex) of the two receptor chains and thereby mediates the association of IRAK with the receptor. Ectopic expression of MyD88 or its death domain-containing N-terminus activates NF-kappaB. The C-terminus of MyD88 interacts with the IL-1 receptor and blocks NF-kappaB activation induced by IL-1, but not by TNF. Thus, MyD88 plays the same role in IL-1 signaling as TRADD and Tube do in TNF and Toll pathways, respectively: it couples a serine/threonine protein kinase to the receptor complex.
Wesche
H
H
Tularik, Incorporated, South San Francisco, California 94080, USA.
Henzel
W J
WJ
Shillinglaw
W
W
Li
S
S
Cao
Z
Z
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D006367:HeLa Cells; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D016296:Mutagenesis; D053594:Myeloid Differentiation Factor 88; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D002352:Carrier Proteins; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D011506:Proteins; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D048029:TNF Receptor-Associated Factor 6; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases