Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling.
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is critical for mediating Toll-like receptor (TLR)-interleukin 1 receptor (IL-1R) signaling and subsequent activation of NF-kappaB and AP-1, transcriptional activators of innate immunity. Here we show that beta-arrestins, a family of multifunctional proteins, directly interacted with TRAF6 after TLR-IL-1R activation. Formation of the ... beta-arrestin-TRAF6 complex prevented autoubiquitination of TRAF6 and activation of NF-kappaB and AP-1. Endotoxin-treated beta-arrestin 2-deficient mice had higher expression of proinflammatory cytokines and were more susceptible to endotoxic shock. Thus, beta-arrestins are essential negative regulators of innate immune activation via TLR-IL-1R signaling.
Mesh Terms:
Animals, Arrestins, Binding Sites, Cell Line, Cytokines, Female, HeLa Cells, Humans, Immunity, Innate, Interleukin-1, Lipopolysaccharides, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B, Signal Transduction, TNF Receptor-Associated Factor 6, Toll-Like Receptor 1, Transcription Factor AP-1, Ubiquitin
Animals, Arrestins, Binding Sites, Cell Line, Cytokines, Female, HeLa Cells, Humans, Immunity, Innate, Interleukin-1, Lipopolysaccharides, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B, Signal Transduction, TNF Receptor-Associated Factor 6, Toll-Like Receptor 1, Transcription Factor AP-1, Ubiquitin
Nat. Immunol.
Date: Feb. 01, 2006
PubMed ID: 16378096
View in: Pubmed Google Scholar
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