IKK related kinases bound to dsRNA:TLR3:TICAM1 activate IRF3

Stable Identifier
Gallus gallus
Related Species
Infectious bronchitis virus
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Cell stimulation with viral ds RNA leads to the activation of two IKK-related serine/threonine kinases, TBK1 and IKK-i which directly phosphorylate IRF3 and IRF7 promoting their dimerization and translocation into the nucleus. Although both kinases show structural and functional similarities, it seems that TBK1 and IKK-i differ in their regulation of downstream signaling events of TLR3.

IRF3 activation and IFN-b production by poly(I:C) are decreased in TBK1-deficient mouse fibroblasts, whereas normal activation was observed in the IKK-i-deficient fibroblasts. However, in double-deficient mouse fibroblasts, the activation of IRF3 is completely abolished, suggesting a partially redundant functions of TBK1 and IKK-i (Hemmi et al. 2004).

TLR3 recruits and activates PI3 kinase (PI3K), which activates the downstream kinase, Akt, leading to full phosphorylation and activation of IRF-3 [Sarkar SN et al 2004]. When PI3K is not recruited to TLR3 or its activity is blocked, IRF-3 is only partially phosphorylated and fails to bind the promoter of the target gene.

Literature References
PubMed ID Title Journal Year
15210742 The roles of two IkappaB kinase-related kinases in lipopolysaccharide and

Takeuchi, O, Hoshino, K, Sanjo, H, Takeda, K, Sato, S, Yamamoto, M, Kaisho, T, Kawai, T, Hemmi, H

J Exp Med 2004
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
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