Reactome: A Curated Pathway Database

TICAM1-dependent activation of IRF3/IRF7

Stable Identifier
R-HSA-9013973
Type
Pathway
Species
Homo sapiens
Related Species
Hepatitis B virus, Rotavirus, Hepatitis C Virus, Influenza A virus, Human herpesvirus 1
Compartment
Synonyms
TLR3-mediated TICAM1-dependent activation of IRF3/IRF7, TLR3-mediated TRIF-dependent activation of IRF3/IRF7, Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
Locations in the PathwayBrowser
Summation

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
Participants
Participant Of
Orthologous Events