Reactome: A Curated Pathway Database

MyD88-independent TLR3/TLR4 cascade (R-HSA-166166)

Species Homo sapiens


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.

Locations in the PathwayBrowser
Additional Information
Compartment cytosol
GO Biological Process MyD88-independent toll-like receptor signaling pathway (0002756)
Cross References
Database Identifier
BioModels Database BIOMD0000000477
Literature References
pubMedId Title Journal Year
15276183 MD-2: the Toll 'gatekeeper' in endotoxin signalling Trends Biochem Sci 2004