Premium
NF‐κB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK‐related kinase
Author(s) -
Pomerantz Joel L.,
Baltimore David
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.23.6694
Subject(s) - tank binding kinase 1 , biology , iκb kinase , traf2 , nfkb1 , kinase , signal transduction , cancer research , microbiology and biotechnology , nf κb , map kinase kinase kinase , genetics , protein kinase a , transcription factor , gene , receptor , tumor necrosis factor receptor
The activation of NF‐κB 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 IκB. TANK is a TRAF‐binding protein that can inhibit the binding of TRAFs to receptor tails and can also inhibit NF‐κB activation by these receptors. However, TANK also displays the ability to stimulate TRAF‐mediated NF‐κB 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‐κB 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‐κB activation but does not block the activation mediated by TNF‐α, 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‐κB.