Toll-like receptor 3 (TLR3) cascade (Homo sapiens)
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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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External references
DataNodes
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Name | Type | Database reference | Comment |
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MyD88-independent TLR3/TLR4 cascade | Pathway | R-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 | Protein | O15455 (Uniprot-TrEMBL) | |
TLR3 | Protein | O15455 (Uniprot-TrEMBL) | |
viral dsRNA | R-VIR-6790593 (Reactome) | ||
viral dsRNA :TLR3 | Complex | R-HSA-167985 (Reactome) | |
viral dsRNA | R-VIR-6790593 (Reactome) |
Annotated Interactions
Source | Target | Type | Database reference | Comment |
---|---|---|---|---|
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. | |||
TLR3 | R-HSA-168092 (Reactome) | |||
viral dsRNA :TLR3 | Arrow | R-HSA-168092 (Reactome) | ||
viral dsRNA | R-HSA-168092 (Reactome) |