The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling

Nat Rev Immunol. 2007 May;7(5):353-64. doi: 10.1038/nri2079.


Signalling by Toll-like receptors (TLRs) involves five adaptor proteins known as MyD88, MAL, TRIF, TRAM and SARM. Recent insights have revealed additional functions for MyD88 apart from NF-kappaB activation, including activation of the transcription factors IRF1, IRF5 and IRF7, and also a role outside the TLRs in interferon-gamma signalling. Biochemical information on MAL and TRAM has shown that both act as bridging adaptors, with MAL recruiting MyD88 to TLR2 and TLR4, and TRAM recruiting TRIF to TLR4 to allow for IRF3 activation. Finally, the function of the fifth adaptor, SARM, has been revealed, which negatively regulates TRIF. These new insights allow for a detailed description of the function of the five TIR-domain-containing adaptors in the initiation of TLR signalling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Adaptor Proteins, Vesicular Transport / physiology*
  • Animals
  • Armadillo Domain Proteins / metabolism
  • Cytoskeletal Proteins / metabolism
  • Humans
  • Myeloid Differentiation Factor 88 / metabolism
  • Signal Transduction / physiology*
  • Toll-Like Receptors / physiology*


  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Armadillo Domain Proteins
  • Cytoskeletal Proteins
  • Myeloid Differentiation Factor 88
  • SARM1 protein, human
  • TICAM1 protein, human
  • TICAM2 protein, human
  • Toll-Like Receptors