Adaptors in toll-like receptor signaling and their potential as therapeutic targets

Thomas Ve, Nicholas Gay, Ashley Scott Mansell, Bostjan Kobe, Stuart Kellie

Research output: Contribution to journalArticleResearchpeer-review

71 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1360 - 1374
Number of pages15
JournalCurrent Drug Targets
Issue number11
Publication statusPublished - 2012

Cite this