Are the IKKs and IKK-related kinases TBK1 and IKK-epsilon similarly activated?

Trends Biochem Sci. 2008 Apr;33(4):171-80. doi: 10.1016/j.tibs.2008.01.002. Epub 2008 Mar 18.

Abstract

The IkappaB kinases (IKKs) IKK-alpha and IKK-beta, and the IKK-related kinases TBK1 and IKK-epsilon, have essential roles in innate immunity through signal-induced activation of NF-kappaB, IRF3 and IRF7, respectively. Although the signaling events within these pathways have been extensively studied, the mechanisms of IKK and IKK-related complex assembly and activation remain poorly defined. Recent data provide insight into the requirement for scaffold proteins in complex assembly; NF-kappaB essential modulator coordinates some IKK complexes, whereas TANK, NF-kappaB-activating kinase-associated protein 1 (NAP1) or similar to NAP1 TBK1 adaptor (SINTBAD) assemble TBK1 and IKK-epsilon complexes. The different scaffold proteins undergo similar post-translational modifications, including phosphorylation and non-degradative polyubiquitylation. Moreover, increasing evidence indicates that distinct scaffold proteins assemble IKK, and potentially TBK1 and IKK-epsilon subcomplexes, in a stimulus-specific manner, which might be a mechanism to achieve specificity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • I-kappa B Kinase / metabolism*
  • I-kappa B Kinase / physiology
  • Models, Biological
  • Models, Genetic
  • NF-kappa B / metabolism
  • Protein Processing, Post-Translational
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / physiology
  • Signal Transduction
  • Ubiquitin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • NF-kappa B
  • SINTBAD protein, human
  • Ubiquitin
  • Protein-Serine-Threonine Kinases
  • TBK1 protein, human
  • I-kappa B Kinase