Reactome | IRF3 is phosphorylated by TBK1

IRF3 is phosphorylated by TBK1

Stable Identifier

R-HSA-2396007

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, cytoplasmic vesicle membrane

ReviewStatus

5/5

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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 Fitzgerald, KA, McWhirter, SM, Faia, KL, Rowe, DC, Latz, E, Golenbock, DT, Coyle, AJ, Liao, SM, Maniatis, T	Nat Immunol	2003
17526488	Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch Panne, D, McWhirter, SM, Maniatis, T, Harrison, SC	J Biol Chem	2007
22394562	STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway Tanaka, Y, Chen, ZJ	Sci Signal	2012