Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction

@article{Fitzgerald2001MalI,
  title={Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction},
  author={Katherine A. Fitzgerald and Eva M. Pålsson-McDermott and Andrew G. Bowie and Caroline A. Jefferies and Ashley Mansell and Gareth Brady and Elizabeth Brint and Aisling Dunne and Pearl Gray and Mary T. Harte and Diane McMurray and Dirk E. Smith and John E. Sims and Timothy A. Bird and Luke A. J. O’Neill},
  journal={Nature},
  year={2001},
  volume={413},
  pages={78-83}
}
The recognition of microbial pathogens by the innate immune system involves Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns, with TLR-4 mediating the response to lipopolysaccharide from Gram-negative bacteria. All TLRs have a Toll/IL-1 receptor (TIR) domain, which is responsible for signal transduction. MyD88 is one such protein that contains a TIR domain. It acts as an adapter, being… 
Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors
TLDR
Differences between signals generated by TLRs are emerging, with both TLR4 and TLR2 signalling requiring an additional adapter termed MyD88-adapter-like (Mal; also known as TIRAP), which may ultimately provide molecular explanations for specificities in the innate immune response to infection.
Investigating TLR-4 signalling in response to protein ligands
TLDR
The aim of this thesis was to determine the stoichiometry of Mal/TIRAP at the plasma membrane of immortalised bone marrow derived macrophages (iBMDMs) and whether this stoichiometric changes upon stimulation with different TLR-4 ligands.
Signalling of toll-like receptors.
TLDR
The TLR pathways can be categorized as MyD88-dependent and TRIF-dependent, based on which pathways will be activated, depending on which of these adapters will be recruited by each TLR.
The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors
TLDR
TIRAP, an adaptor protein in the TLR signalling pathway, has been identified and shown to function downstream of TLR4 and may account for specificity in the downstream signalling of individual TLRs.
MyD88 Adapter-like (Mal) Is Phosphorylated by Bruton's Tyrosine Kinase during TLR2 and TLR4 Signal Transduction*
TLDR
This study provides the first demonstration of the key role of Mal phosphorylation on tyrosine during signaling by TLR2 and TLR4 and identifies a novel function for Btk as the kinase involved.
TRAM is specifically involved in the Toll-like receptor 4–mediated MyD88-independent signaling pathway
TLDR
TRAM provides specificity for the MyD88-independent component of TLR4 signaling, and is identified as a fourth TIR domain–containing adaptor, TRIF-related adaptor molecule (TRAM), and analyzed its physiological function by gene targeting.
Microbial recognition by Toll-like receptors.
Toll-like Receptors and Their Signaling Mechanisms
TLDR
Characterization of each TLR signaling pathway will reveal the molecular mechanism of self-t tolerance as well as cross-tolerance in response to a variety of PAMPs.
TIR domain-containing adaptors regulate TLR signaling pathways.
TLDR
Accumulating evidence clearly demonstrates that Toll-like receptors serve as pattern recognition receptors to detect invading microbes.
Role of adapters in Toll-like receptor signalling.
TLDR
Evidence is now accumulating showing that differential utilization of these adaptors may activate overlapping as well as distinct signalling pathways, and ultimately give rise to distinct biological effects exerted by individual TLR family members.
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