NF-κB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase

被引:484
作者
Pomerantz, JL [1 ]
Baltimore, D [1 ]
机构
[1] CALTECH, Div Geol, Pasadena, CA 91125 USA
关键词
IKK; NF-kappa B; TANK; TBK1; TRAF2;
D O I
10.1093/emboj/18.23.6694
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The activation of NF-kappa B by receptors in the tumor necrosis factor (TNF) receptor and Toll/interleukin-1 (IL-1) receptor families requires the TRAF family of adaptor proteins. Receptor oligomerization causes the recruitment of TRAFs to the receptor complex, followed by the activation of a kinase cascade that results in the phosphorylation of I kappa B. TANK is a TRAF-binding protein that can inhibit the binding of TRAFs to receptor tails and can also inhibit NF-kappa B activation by these receptors, However, TANK also displays the ability to stimulate TRAF-mediated NF-kappa B activation, In this report, we investigate the mechanism of the stimulatory activity of TANK, We find that TANK interacts with TBK1 (TANK-binding kinase 1), a novel IKK-related kinase that can activate NF-kappa B in a kinase-dependent manner. TBK1, TANK and TRAF2 can form a ternary complex, and complex formation appears to be required for TBK1 activity. Kinase-inactive TBK1 inhibits TANK-mediated NF-kappa B activation but does not block the activation mediated by TNF-alpha, IL-1 or CD40. The TBK1-TANK-TRAF2 signaling complex functions upstream of NIK and the IKK complex and represents an alternative to the receptor signaling complex for TRAF-mediated activation of NF-kappa B.
引用
收藏
页码:6694 / 6704
页数:11
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