Association of β-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling

Yaya Wang, Yawei Tang, Lin Teng, Yalan Wu, Xiaohui Zhao, Gang Pei

Research output: Contribution to journalArticlepeer-review

198 Scopus citations

Abstract

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-κB and AP-1, transcriptional activators of innate immunity. Here we show that β-arrestins, a family of multifunctional proteins, directly interacted with TRAF6 after TLR -IL-1R activation. Formation of the β-arrestin-TRAF6 complex prevented autoubiquitination of TRAF6 and activation of NF-κB and AP-1. Endotoxin-treated β-arrestin 2-deficient mice had higher expression of proinflammatory cytokines and were more susceptible to endotoxic shock. Thus, β-arrestins are essential negative regulators of innate immune activation via TLR-IL-1R signaling.

Original languageEnglish (US)
Pages (from-to)139-147
Number of pages9
JournalNature immunology
Volume7
Issue number2
DOIs
StatePublished - Feb 2006

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