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Handb Exp Pharmacol. 2008;(183):21-50.

Signalling of toll-like receptors.

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School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.


Since Toll-like receptor (TLR) signaling was found crucial for the activation of innate and adaptive immunity, it has been the focus of immunological research. There are at least 13 identified mammalian TLRs, to date, that share similarities in their extracellular and intracellular domains. A vast number of ligands have been identified that are specifically recognized by different TLRs. As a response the TLRs dimerize and their signaling is initiated. The molecular basis of that signaling depends on the conserved part of their intracellular domain; namely the Toll/IL-1 receptor (TIR) domain. Upon TLR dimerization a TIR-TIR structure is formed that can recruit TIR-containing intracellular proteins that mediate their signaling. For this reason these proteins are named adapters. There are five adapters identified so far named myeloid differentiation primary response protein 88 (MyD88), MyD88-adapter like (Mal) or TIR domain-containing adapter (TIRAP), TIR domain-containing adapter inducing interferon-beta (IFN-beta) (TRIF) or TIR-containing adapter molecule-1 (TICAM-1), TRIF-related adapter molecule (TRAM) or TICAM-2, and sterile alpha and HEAT-Armadillo motifs (SARM). The first four play a fundamental role in TLR-signaling, defining which pathways will be activated, depending on which of these adapters will be recruited by each TLR. Among these adapter proteins MyD88 and TRIF are now considered as the signaling ones and hence the TLR pathways can be categorized as MyD88-dependent and TRIF-dependent.

[Indexed for MEDLINE]

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