The cytoplasmic domain of the interleukin-1 receptor is required for nuclear factor-kappa B signal transduction.

Interleukin-1 (IL-1) plays a central role in mediating immune and inflammatory responses. Binding of IL-1 to the type I 80-kDa receptor results in generation of intracellular signals and activation of the transcription factor NF-kappa B. However, the nature of the signals required to generate NF-kappa B binding activity remains unclear. In this paper, we show that NF-kappa B1 (p50) and RelA (p65) were specifically translocated to the nucleus following activation of intact type I IL-1 receptor (IL-1R). The C-terminal region of the type I IL-1R is required for this effect, and deletion of its cytoplasmic domain abrogates the activation of NF-kappa B by IL-1. These results provide evidence that IL-1 modulates the activity of NF-kappa B through the type I IL-1 receptor and identifies a domain required for signal transduction to this specific transcription factor.