IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway

Nat Immunol. 2003 May;4(5):491-6. doi: 10.1038/ni921.

Abstract

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.

Publication types

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

MeSH terms

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

Substances

  • Adaptor Proteins, Vesicular Transport
  • Chemokine CCL5
  • DNA-Binding Proteins
  • Drosophila Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Cell Surface
  • TICAM1 protein, human
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptors
  • Transcription Factors
  • Interferon-beta
  • Protein-Serine-Threonine Kinases
  • TBK1 protein, human
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human