Nature Immunology 7, 139 - 147 (2005)
Published online: 25 December 2005; | doi:10.1038/ni1294
Association of  -arrestin and TRAF6 negatively regulates Toll-like receptor–interleukin 1 receptor signalingYaya Wang, Yawei Tang, Lin Teng, Yalan Wu, Xiaohui Zhao
& Gang Pei
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Graduate School of the Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
Correspondence should be addressed to Gang Pei gpei@sibs.ac.cn 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- B and AP-1, transcriptional activators of innate immunity. Here we show that  -arrestins, a family of multifunctional proteins, directly interacted with TRAF6 after TLR–IL-1R activation. Formation of the -arrestin–TRAF6 complex prevented autoubiquitination of TRAF6 and activation of NF-B and AP-1. Endotoxin-treated -arrestin 2–deficient mice had higher expression of proinflammatory cytokines and were more susceptible to endotoxic shock. Thus, -arrestins are essential negative regulators of innate immune activation via TLR–IL-1R signaling.
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