Reactome: A Curated Pathway Database

Toll-Like Receptors Cascades (R-HSA-168898)

Species Homo sapiens

Summation

In human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) domain in their cytoplasmic region and an Ig-like domain in the extracellular region, where each is enriched with a varying number of leucine-rich repeats (LRRs). Each TLR can recognize specific microbial pathogen components. The binding pathogenic component to TLR initializes signaling pathways that lead to induction of Interferon alpha/beta and inflammatory cytokines. There are two main signaling pathways. The first is a MyD88-dependent pathway that is common to all TLRs, except TLR3; the second is a TRIF(TICAM1)-dependent pathway that is peculiar to TLR3 and TLR4. TLR4-mediated signaling pathway via TRIF requires adapter molecule TRAM (TRIF-related adapter molecule or TICAM2). TRAM is thought to bridge between the activated TLR4 complex and TRIF.(Takeda & Akira 2004; Akira 2003; Takeda & Akira 2005; Kawai 2005; Heine & Ulmer 2005).

Locations in the PathwayBrowser
Additional Information
GO Biological Process toll-like receptor signaling pathway (0002224)
Literature References
pubMedId Title Journal Year
14751757 TIR domains, which are conserved among all TLRs. Recent accumulating Semin Immunol 2004
12893815 Toll-like receptor signaling J Biol Chem 2003
15585605 TIRAP/Mal, TRIF and TRAM. Differential utilization of these TIR Int Immunol 2005
15950447 Pathogen recognition with Toll-like receptors Curr Opin Immunol 2005
15976490 Recognition of bacterial products by toll-like receptors Chem Immunol Allergy 2005