IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway
Immunology & Virology Program
Department of Medicine, Division of Infectious Diseases and Immunology
Medical Subject Headings
Adaptor Proteins, Vesicular Transport; Chemokine CCL5; DNA-Binding Proteins; *Drosophila Proteins; Gene Expression Regulation; Humans; I-kappa B Kinase; Immunity, Natural; 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
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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.
Rights and Permissions
Citation: Nat Immunol. 2003 May;4(5):491-6. Link to article on publisher's site
Fitzgerald, Katherine A.; McWhirter, Sarah M.; Faia, Kerrie L.; Rowe, Daniel C.; Latz, Eicke; Golenbock, Douglas T.; Coyle, Anthony J.; Liao, Sha-Mei; and Maniatis, Tom, "IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway" (2003). GSBS Student Publications. Paper 291.