Toll-like receptor 4 signalling: new perspectives on a complex signal-transduction problem
Related Experiment Video
Updated: Sep 25, 2026

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation
Published on: September 7, 2010
1Department of Microbiology and Immunology, and Department of Medicine, University of Maryland, Baltimore, 655 W. Baltimore Street 13-009, Baltimore, MD 21201, USA. svogel@som.umaryland.edu
Abstract:
We previously reported that Toll-like receptor-2 (TLR2) agonists induce expression of a more limited repertoire of pro-inflammatory genes than TLR4 agonists. Murine macrophages stimulated with the TLR4 agonist, Escherichia coli lipopolysaccharide, induced signal transducer and activator of transcription 1 ('STAT1') tyrosine phosphorylation that was secondary to the autocrine/paracrine action of interferon (IFN)-beta, an immediate early gene. In contrast, TLR2 agonists failed to activate IFN-beta gene expression. TLR4-induced IFN-beta mRNA was found to be MyD88- and PKR (double-stranded RNA-dependent protein kinase)-independent, but TIRAP (Toll/interleukin-1 receptor domain-containing adapter protein)/Mal (MyD88-adapter-like)-dependent. In the present paper, we outline the recent controversy over the role of TIRAP/Mal in TLR2 and TLR4 signalling in the context of the current molecular tools used for such studies. Collectively, our findings provide the first mechanistic basis for differential patterns of gene expression activated by TLR4 and TLR2 agonists.
More Related Videos
Related Concept Videos
Amplifying Signals via Second Messengers
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Amplifying Signals via Enzymatic Cascade
Receptor Tyrosine Kinases
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:

