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

Pomerantz, Joel L. and Baltimore, David (1999) NF-κB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO Journal, 18 (23). pp. 6694-6704. ISSN 1460-2075. PMCID PMC1171732. doi:10.1093/emboj/18.23.6694.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle
Baltimore, David0000-0001-8723-8190
Additional Information:© 1999 European Molecular Biology Organization. Received July 28, 1999; revised September 30, 1999; accepted October 4, 1999. We thank members of the Baltimore laboratory for helpful discussions and support, I. Stancovski, X. Yang, Y.H. Li, G. Cohen, B. Chen, R. Khosravi‐Far, Z. Cao, D. Goeddell, W. Greene, C. Janeway and D. Wallach for reagents, and A. Greenwood, J. Kim, L. Van Parijs, D. Van Antwerp, C. Lois and I. Stancovski for critical reading of the manuscript. We also thank G. Cheng, T. Kawai, S. Akira, R. Peters and T. Maniatis for communication of results prior to publication. J.L.P. is supported by a postdoctoral fellowship from the Helen Hay Whitney Foundation. This work was supported by the NIH grant AI42549‐02.
Funding AgencyGrant Number
Helen Hay Whitney FoundationUNSPECIFIED
Subject Keywords:IKK/NF-κB/TANK/TBK1/TRAF2
Issue or Number:23
PubMed Central ID:PMC1171732
Record Number:CaltechAUTHORS:20200506-145226410
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Official Citation:Pomerantz, J.L. and Baltimore, D. (1999), NF‐κB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK‐related kinase. The EMBO Journal, 18: 6694-6704. doi:10.1093/emboj/18.23.6694
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103048
Deposited By: Tony Diaz
Deposited On:06 May 2020 22:05
Last Modified:16 Nov 2021 18:17

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