title: IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.
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.
authors.affiliation: Division of Infectious Disease & Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.forename: Sarah M
authors.initials: SM
authors.lastname: McWhirter
authors.forename: Kerrie L
authors.initials: KL
authors.lastname: Faia
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Rowe
authors.forename: Eicke
authors.initials: E
authors.lastname: Latz
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Sha-Mei
authors.initials: SM
authors.lastname: Liao
authors.forename: Tom
authors.initials: T
authors.lastname: Maniatis
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000235:genetics; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism*; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018946:Chemokine CCL5; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C470409:TICAM1 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D014157:Transcription Factors; D016899:Interferon-beta; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human