Toll-like receptor 3 (TLR3) cascade (Homo sapiens)

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1, 5, 86, 7cytosolendosomeTLR3 viral dsRNA :TLR3viral dsRNA TLR3viral dsRNAMyD88-independentTLR3/TLR4 cascade 42, 3


Description

Toll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and inflammatory responses of the innate immunity in combating viral infections.

Mammalian TLR3 recognizes dsRNA, and that triggers the receptor to induce the activation of NF-kappaB and the production of type I interferons (IFNs). dsRNA-stimulated phosphorylation of two specific TLR3 tyrosine residues (Tyr759 and Tyr858) is essential for initiating TLR3 signaling pathways. View original pathway at:Reactome.</div>

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History

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CompareRevisionActionTimeUserComment
116523view11:05, 7 May 2021EweitzModified title
114807view16:30, 25 January 2021ReactomeTeamReactome version 75
113251view11:32, 2 November 2020ReactomeTeamReactome version 74
112469view15:42, 9 October 2020ReactomeTeamReactome version 73
101378view11:26, 1 November 2018ReactomeTeamreactome version 66
100916view21:01, 31 October 2018ReactomeTeamreactome version 65
100457view19:36, 31 October 2018ReactomeTeamreactome version 64
100004view16:20, 31 October 2018ReactomeTeamreactome version 63
99557view14:53, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99186view12:42, 31 October 2018ReactomeTeamreactome version 62
93762view13:34, 16 August 2017ReactomeTeamreactome version 61
93286view11:19, 9 August 2017ReactomeTeamreactome version 61
88401view15:21, 4 August 2016FehrhartOntology Term : 'Toll-like receptor signaling pathway' added !
86370view09:16, 11 July 2016ReactomeTeamreactome version 56
83334view10:49, 18 November 2015ReactomeTeamVersion54
81488view13:01, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
MyD88-independent TLR3/TLR4 cascade PathwayR-HSA-166166 (Reactome) MyD88-independent signaling pathway is shared by TLR3 and TLR4 cascades. TIR-domain-containing adapter-inducing interferon-beta (TRIF or TICAM1) is a key adapter molecule in transducing signals from TLR3 and TLR4 in a MyD88-independent manner (Yamamoto M et al. 2003a). TRIF is recruited to ligand-stimulated TLR3 or 4 complex via its TIR domain. TLR3 directly binds TRIF (Oshiumi H et al 2003). In contrast, TLR4-mediated signaling pathway requires two adapter molecules, TRAM (TRIF-related adapter molecule or TICAM2) and TRIF. TRAM(TICAM2) is thought to bridge between the activated TLR4 complex and TRIF (Yamamoto M et al. 2003b, Tanimura N et al. 2008, Kagan LC et al. 2008).

TRIF recruitment to TLR complex stimulates distinct pathways leading to production of type 1 interferons (IFNs), pro-inflammatory cytokines and induction of programmed cell death.

TLR3 ProteinO15455 (Uniprot-TrEMBL)
TLR3ProteinO15455 (Uniprot-TrEMBL)
viral dsRNA R-VIR-6790593 (Reactome)
viral dsRNA :TLR3ComplexR-HSA-167985 (Reactome)
viral dsRNAR-VIR-6790593 (Reactome)

Annotated Interactions

SourceTargetTypeDatabase referenceComment
R-HSA-168092 (Reactome) Viral dsRNA triggers an antiviral pathway mediated by toll like receptor 3. TLR3 dimerization occurs upon ligand binding to positivly charged residues on the ectodomain termini of TLR3 wich are responsible for the interaction with sugar-phosphate groups of dsRNA.
TLR3R-HSA-168092 (Reactome)
viral dsRNA :TLR3ArrowR-HSA-168092 (Reactome)
viral dsRNAR-HSA-168092 (Reactome)

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