description
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

external resources
NCBI:1269222
REACTOME:R-HSA-936964
PUBMED:15210742
PUBMED:14679297
PUBMED:15502848
PUBMED:17332413

genes
CD14 , IRF3 , IRF7 , PTPN11 , RPS27A , TLR3 , TLR4 , TRAF3 , UBA52 , UBB , UBC , IKBKE , TANK , SARM1 , LY96 , TBK1 , TICAM1 , TICAM2 ,