NF-KAPPA-B ACTIVATION BY INTERLEUKIN-1 (IL-1) REQUIRES AN IL-1 RECEPTOR-ASSOCIATED PROTEIN-KINASE ACTIVITY

An important function of interleukin-1 (IL-1) is activation of the transcription factor NF-kappa B, which is signaled via the type I IL-1 receptor (IL-1RI), By receptor mutagenesis studies, we have identified a region of the cytoplasmic domain of IL-1RI that is required for both IL-1-mediated NF-kappa B activation and IL-1-dependent activation of a receptor-associated protein kinase activity we term IRAK. No IL-1RI mutants were found that can activate NF-kappa B in the absence of IRAK activity, Therefore, we propose that IRAK activation is a necessary step in the activation of NF-kappa B by IL-1.