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

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

Authors

  • Fitzgerald KA
  • McWhirter SM
  • Faia KL
  • Rowe DC
  • Latz E
  • Golenbock DT
  • Coyle AJ
  • Liao SM
  • Maniatis T

Journal

Nature immunology

Publication Data

May 29, 2003

Associated Grants

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

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