Reactome | Phosphorylation of IRF3 by TBK1 complexed with activated TLR3

Phosphorylation of IRF3 by TBK1 complexed with activated TLR3

Stable Identifier

R-GGA-433786

Type

Reaction [transition]

Species

Gallus gallus

Compartment

cytosol, endosome membrane

ReviewStatus

5/5

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Phosphorylation of IRF3 by TBK1 complexed with activated TLR3

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IRF-3 is activated by two step phosphorylation. IKK related kinases TBK1 and/or IKKi mediate the phosphorylation of the residues Ser386 and/or Ser385 (site1) and a cluster of serine/threonine residues between Ser396 and Ser405 (site 2) [Panne et al 2007]. Phosphorylation of residues in site 2 alleviates autoinhibition to allow interaction with CBP (CREB-binding protein) and facilitates phosphorylation at site 1. Phosphorylation at site 1 is required for IRF-3 dimerization.

All serine residues mentioned above were empirically defined for human IRF3. Multiple sequence alignment of human, mouse and chicken IRF3 by ClustalW showed similarity in the C-terminal domain and the following chicken residues are predicted to be involved in chicken IRF3 activation:

Ser463 and/or Ser464 (site 1, corresponding to human Ser385 and Ser386)
Ser474 and Ser476 (site2,corresponding to human Ser396 and Ser398 from the cluster of Ser396-Ser405)

Literature References

PubMed ID	Title	Journal	Year
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
14703513	Identification of Ser-386 of interferon regulatory factor 3 as critical Fujita, T, Inagaki, F, Takahashi, K, Yoneyama, M, Mori, M, Ito, T	J Biol Chem	2004
9463386	Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300 Nishida, E, Fukuda, M, Suhara, W, Fujita, T, Fukuhara, Y, Yoneyama, M	EMBO J	1998