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.
Leung
K
K
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109-0650.
Betts
J C
JC
Xu
L
L
Nabel
G J
GJ
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015458:Leukemia, T-Cell; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism*; D015183:Restriction Mapping; D017384:Sequence Deletion; D015398:Signal Transduction; D051996:Transcription Factor RelA; D014162:Transfection; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D017472:Receptors, Interleukin-1; D051996:Transcription Factor RelA