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biopax3:comment |
Authored: Shamovsky, V, 2010-06-01,
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.<p>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].<p>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.,
Edited: Shamovsky, V, 2010-11-16,
Reviewed: Gillespie, ME, 2010-11-30
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biopax3:xref |
http://identifiers.org/pubmed/14679297,
http://identifiers.org/pubmed/15210742,
http://identifiers.org/pubmed/15502848,
http://identifiers.org/pubmed/17332413,
urn:biopax:RelationshipXref:GENE ONTOLOGY_GO:0035666,
urn:biopax:UnificationXref:REACTOME DATABASE ID_936964,
urn:biopax:UnificationXref:REACTOME_REACT_25148_3
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biopax3:dataSource | |
biopax3:displayName |
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
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biopax3:organism | |
biopax3:pathwayComponent |
http://www.reactome.org/biopax/48887BiochemicalReaction2510,
http://www.reactome.org/biopax/48887BiochemicalReaction2511,
http://www.reactome.org/biopax/48887BiochemicalReaction2512,
http://www.reactome.org/biopax/48887BiochemicalReaction2513,
http://www.reactome.org/biopax/48887BiochemicalReaction2514,
http://www.reactome.org/biopax/48887BiochemicalReaction2515,
http://www.reactome.org/biopax/48887BiochemicalReaction2516
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biopax3:pathwayOrder |
http://www.reactome.org/biopax/48887PathwayStep3213,
http://www.reactome.org/biopax/48887PathwayStep3219,
http://www.reactome.org/biopax/48887PathwayStep3214,
http://www.reactome.org/biopax/48887PathwayStep3215,
http://www.reactome.org/biopax/48887PathwayStep3218,
http://www.reactome.org/biopax/48887PathwayStep3216,
http://www.reactome.org/biopax/48887PathwayStep3217
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