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IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.

Nature immunology | May 29, 2003

The transcription factors interferon regulatory factor 3 (IRF3) and NF-kappaB are required for the expression of many genes involved in the innate immune response. Viral infection, or the binding of double-stranded RNA to Toll-like receptor 3, results in the coordinate activation of IRF3 and NF-kappaB. Activation of IRF3 requires signal-dependent phosphorylation, but little is known about the signaling pathway or kinases involved. Here we report that the noncanonical IkappaB kinase homologs, IkappaB kinase-epsilon (IKKepsilon) and TANK-binding kinase-1 (TBK1), which were previously implicated in NF-kappaB activation, are also essential components of the IRF3 signaling pathway. Thus, IKKepsilon and TBK1 have a pivotal role in coordinating the activation of IRF3 and NF-kappaB in the innate immune response.

Pubmed ID: 12692549 RIS Download

Mesh terms: Adaptor Proteins, Vesicular Transport | Chemokine CCL5 | DNA-Binding Proteins | Drosophila Proteins | Gene Expression Regulation | Humans | I-kappa B Kinase | Immunity, Innate | Interferon Regulatory Factor-3 | Interferon-beta | Membrane Glycoproteins | NF-kappa B | Protein-Serine-Threonine Kinases | RNA Interference | Receptors, Cell Surface | Signal Transduction | Toll-Like Receptor 3 | Toll-Like Receptors | Transcription Factors | Virus Diseases

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Associated grants

  • Agency: NIAID NIH HHS, Id: R01 AI20642
  • Agency: NIGMS NIH HHS, Id: R01 GM54060

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