MYD88 - AN ADAPTER THAT RECRUITS IRAK TO THE IL-1 RECEPTOR COMPLEX

IL-1 is a proinflammatory cytokine that signals through a receptor com plex of two different transmembrane chains to generate multiple cellul ar responses, including activation of the transcription factor NF-kapp a B. Here we show that MyD88, a previously described protein of unknow n function, is recruited to the IL-l receptor complex following IL-l s timulation. MyD88 binds to both IRAK (IL-l receptor-associated kinase) and the heterocomplex (the signaling complex) of the two receptor cha ins and thereby mediates the association of IRAK with the receptor. Ec topic expression of MyD88 or its death domain-containing N-terminus ac tivates NF-kappa B. The C-terminus of MyD88 interacts with the IL-l re ceptor and blocks NF-kappa B activation induced by IL-l, but not by TN F. Thus, MyD88 plays the same role in IL-l signaling as TRADD and Tube do in TNF and Toll pathways, respectively: it couples a serine/threon ine protein kinase to the receptor complex.