Structure and function of the intracellular portion of the mouse interleukin 1 receptor (type I). Determining the essential region for transducing signals to activate the interleukin 8 gene

Abstract

The structural and functional relationships of the intracellular portion of mouse interleukin 1 receptor (muIL-1R) type I were examined with regard to activation of the human IL-8 gene in the Jurkat T cell line. C-terminal deletion mutations of muIL-1R revealed that the C-terminal boundary for receptor function is localized between 28 and 42 amino acids from the C-terminal end. The internal deletion mutants between amino acids 364 and 474 had a loss of activity, demonstrating the requirement for a large region of the mIL-1R cytoplasmic portion for receptor function. Amino acid substitution revealed that the putative nuclear localization elements (amino acids at 429-433, 523-527, and 507-519) and putative protein kinase C or A acceptor sites (Ser-431, Ser-509, Ser-528) do not participate in IL-1 signaling to induce IL-8 gene expression. A truncated mutation within the segment, which possesses homology with gp130, beta chain of IL-6R, or a point mutation of box 1- and box 2-like elements within the gp130 homologous segment, abolished the capacity to induce IL-8 gene expression, suggesting similar structural requirements in the cytoplasmic portion of several cytokine receptors.