NF-κB Activation by Interleukin-1 (IL-1) Requires an IL-1 Receptor-associated Protein Kinase Activity

Abstract An important function of interleukin-1 (IL-1) is activation of the transcription factor NF-κB, 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-κB 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-κB in the absence of IRAK activity. Therefore, we propose that IRAK activation is a necessary step in the activation of NF-κB by IL-1.