RECRUITMENT OF IRAK TO THE INTERLEUKIN-1 RECEPTOR COMPLEX REQUIRES INTERLEUKIN-1 RECEPTOR ACCESSORY PROTEIN

The proinflammatory cytokine interleukin 1 (IL-1) activates the transc ription of many genes encoding acute phase and proinflammatory protein s, a function mediated primarily by the transcription factor NF-kappa B. An early IL-1 signaling event is the recruitment of the Ser/Thr kin ase IRAK to the type I IL-1 receptor (IL-1RI). Here we describe the fu nction of a previously identified IL-1 receptor subunit designated IL- 1 receptor accessory protein (IL-1RAcP). IL-1 treatment of cells induc es the formation of a complex containing both IL-1RI and IL-1RAcP. IRA K 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 rec eptor complex and blocked IL-1-induced NF-kappa B activation.