Phosphorylation and release of IRF3

Stable Identifier
R-GGA-1227881
Type
Reaction [transition]
Species
Gallus gallus
Related Species
Infectious bronchitis virus
Compartment
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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

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

J Biol Chem 2007
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
10893229 Multiple regulatory domains control IRF-7 activity in response to virus infection

Lin, R, Mamane, Y, Hiscott, J

J Biol Chem 2000
16914100 Induction of IRF-3 and IRF-7 phosphorylation following activation of the RIG-I pathway

Paz, S, Sun, Q, Nakhaei, P, Romieu-Mourez, R, Goubau, D, Julkunen, I, Lin, R, Hiscott, J

Cell Mol Biol (Noisy-le-grand) 2006
9463386 Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300

Yoneyama, M, Suhara, W, Fukuhara, Y, Fukuda, M, Nishida, E, Fujita, T

EMBO J 1998
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of dsRNA:MDA5:IPS1:K63 pUb-TRAF3/or TRAF6:TANK:activated TBK1/or IKK epsilon: IRF3 [mitochondrial outer membrane]
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Activity
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