Reactome | Toll-like Receptor Cascades

Toll-like Receptor Cascades

Stable Identifier

R-HSA-168898

Type

Pathway

Species

Homo sapiens

Related Species

Toxoplasma gondii, Influenza A virus, Rotavirus, Hepatitis B virus, Hepatitis C Virus, Chlamydia trachomatis, Human herpesvirus 1, Escherichia coli, Neisseria meningitidis serogroup B

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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). This pathway is organized as trafficking and processing of TLR, various TLR cascades (TLR10,TLR3,TLR5,TLR7/8,TLR9,TLR4,TLR2) and their regulation.

Literature References

PubMed ID	Title	Journal	Year
14751757	TIR domains, which are conserved among all TLRs. Recent accumulating Takeda, K, Akira, S	Semin Immunol	2004
15976490	Recognition of bacterial products by toll-like receptors Ulmer, AJ, Heine, H	Chem Immunol Allergy	2005
15585605	TIRAP/Mal, TRIF and TRAM. Differential utilization of these TIR Takeda, K, Akira, S	Int Immunol	2005
15950447	Pathogen recognition with Toll-like receptors Kawai, T	Curr Opin Immunol	2005
12893815	Toll-like receptor signaling Akira, S	J Biol Chem	2003