Abstract
To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group. Other TIR domain-containing proteins have also been shown to regulate these signaling pathways, including ST2 and SIGIRR, as well as several bacterial and viral TIR domain-containing proteins that modulate these pathways as virulence factors. TLR pathways and the adaptor proteins are associated with a number of diseases, including infection, sepsis, inflammatory, allergic and autoimmune diseases and cancer. We review our current understanding of the structure and function of adaptor proteins and their regulatory proteins, their association with disease and their potential as therapeutic targets in human disease.
Keywords: Toll-like receptors (TLRs), TIR (Toll/interleukin-1 receptor) domain, adaptor proteins, Therapeutic Targets, signaling adaptor proteins, PAMPs, ligand-receptor interaction, ST2, SIGIRR, signaling pathways.
Current Drug Targets
Title:Adaptors in Toll-Like Receptor Signaling and their Potential as Therapeutic Targets
Volume: 13 Issue: 11
Author(s): Thomas Ve, Nicholas J. Gay, Ashley Mansell, Bostjan Kobe and Stuart Kellie
Affiliation:
Keywords: Toll-like receptors (TLRs), TIR (Toll/interleukin-1 receptor) domain, adaptor proteins, Therapeutic Targets, signaling adaptor proteins, PAMPs, ligand-receptor interaction, ST2, SIGIRR, signaling pathways.
Abstract: To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group. Other TIR domain-containing proteins have also been shown to regulate these signaling pathways, including ST2 and SIGIRR, as well as several bacterial and viral TIR domain-containing proteins that modulate these pathways as virulence factors. TLR pathways and the adaptor proteins are associated with a number of diseases, including infection, sepsis, inflammatory, allergic and autoimmune diseases and cancer. We review our current understanding of the structure and function of adaptor proteins and their regulatory proteins, their association with disease and their potential as therapeutic targets in human disease.
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Cite this article as:
Ve Thomas, J. Gay Nicholas, Mansell Ashley, Kobe Bostjan and Kellie Stuart, Adaptors in Toll-Like Receptor Signaling and their Potential as Therapeutic Targets, Current Drug Targets 2012; 13 (11) . https://dx.doi.org/10.2174/138945012803530260
DOI https://dx.doi.org/10.2174/138945012803530260 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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