IRF3 is phosphorylated by TBK1

Stable Identifier
Reaction [transition]
Homo sapiens
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IRF3 is activated through a two-step phosphorylation in the C-terminal domain mediated by TBK1 and/or IKKi, requiring Ser386 and/or Ser385- site 1; and a cluster of serine/threonine residues between Ser396 and Ser405- site 2 [Panne et al 2007]. Phosphorylated residues at site 2 (Ser396 - Ser405) alleviate autoinhibition to allow interaction with CBP (CREB-binding protein) and facilitate phosphorylation at site 1 (Ser385 or Ser386). Phosphorylation at site 1 is required for IRF3 dimerization.

Literature References
PubMed ID Title Journal Year
12692549 IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway

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

Nat Immunol 2003
17526488 Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch

McWhirter, SM, Maniatis, T, Harrison, SC, Panne, D

J Biol Chem 2007
22394562 STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway

Tanaka, Y, Chen, ZJ

Sci Signal 2012
Catalyst Activity

protein serine/threonine kinase activity of STING:p-S172-TBK1:IRF3 [cytoplasmic vesicle membrane]

This event is regulated