ArticleMolecular and cellular biology2003
Common interaction surfaces of the toll-like receptor 4 cytoplasmic domain stimulate multiple nuclear targets.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- TLR4 phosphorylation at tyrosine 672 activates the ERK/c-FOS signaling module for LPS-induced cytokine responses in macrophages.European journal of immunology · 2023Article
- Full-Atom Model of the Agonist LPS-Bound Toll-like Receptor 4 Dimer in a Membrane Environment.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Peptidoglycan Switches Off the TLR2-Mediated Sperm Recognition and Triggers Sperm Localization in the Bovine Endometrium.Frontiers in immunology · 2020Article
- Toll-Like Receptor Evolution in Birds: Gene Duplication, Pseudogenization, and Diversifying Selection.Molecular biology and evolution · 2018Article
- SCIMP is a transmembrane non-TIR TLR adaptor that promotes proinflammatory cytokine production from macrophages.Nature communications · 2017Article
- Three conserved MyD88-recruiting TLR residues exert different effects on the human TLR4 signaling pathway.Immunologic research · 2015Article
- Activation of c-Src: a hub for exogenous pro-oxidant-mediated activation of Toll-like receptor 4 signaling.Free radical biology & medicine · 2014Article
- TLR4, IL10RA, and NOD2 mutation in paediatric Crohn's disease patients: an association with Mycobacterium avium subspecies paratuberculosis and TLR4 and IL10RA expression.Medical microbiology and immunology · 2013Article
- Molecular mechanisms for the subversion of MyD88 signaling by TcpC from virulent uropathogenic Escherichia coli.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Suppression of TLR signaling by targeting TIR domain-containing proteins.Current protein & peptide science · 2012Review
- Poxviral protein A46 antagonizes Toll-like receptor 4 signaling by targeting BB loop motifs in Toll-IL-1 receptor adaptor proteins to disrupt receptor:adaptor interactions.The Journal of biological chemistry · 2012Article
- Identification of interaction sites for dimerization and adapter recruitment in Toll/interleukin-1 receptor (TIR) domain of Toll-like receptor 4.The Journal of biological chemistry · 2012Article
- Effects of 15-deoxy-∆¹²,¹⁴-prostaglandin J₂ on the production of IL-8 and the expression of Toll-like receptor 2 in human primary keratinocytes stimulated with lipopolysaccharide.Molecular biology reports · 2011Article
- Targeting TLR4 signaling by TLR4 Toll/IL-1 receptor domain-derived decoy peptides: identification of the TLR4 Toll/IL-1 receptor domain dimerization interface.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- TIR domain-containing adaptor SARM is a late addition to the ongoing microbe-host dialog.Developmental and comparative immunology · 2011Article
- In silico approach to inhibition of signaling pathways of Toll-like receptors 2 and 4 by ST2L.PloS one · 2011Article
- Molecular mimicry in innate immunity: crystal structure of a bacterial TIR domain.The Journal of biological chemistry · 2009Article
- Differential role for c-Rel and C/EBPbeta/delta in TLR-mediated induction of proinflammatory cytokines.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- The LPS-induced transcriptional upregulation of the chicken lysozyme locus involves CTCF eviction and noncoding RNA transcription.Molecular cell · 2008Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Toll-like receptor 4 (TLR4) mediates the host response to lipopolysaccharide (LPS) by promoting the activation of pro- and anti-inflammatory cytokine genes. To activate each gene, numerous signal transduction pathways are required. The adaptor proteins MyD88 and TIRAP contribute to the activation of several and possibly all pathways via direct interactions with TLR4's Toll/interleukin-1 receptor (IL-1R) (TIR) domain. However, additional adaptors that are required for the activation of specific subsets of pathways may exist, which could contribute to the differential regulation of target genes. Furthermore, it remains unknown whether direct interactions that have been reported between TIR domains and other proteins are required for TLR4 signaling. To address these issues, we systematically mutated the TLR4 TIR domain in the context of a CD4/TLR4 fusion protein. Several exposed residues defining at least two structural surfaces were required in macrophages for activation of the proinflammatory IL-12 p40 and anti-inflammatory IL-10 promoters, as well as promoters dependent on individual transcription factors. Interestingly, the same residues were required by all promoters tested, suggesting that the signaling pathways diverge downstream of the adaptors. The mutant phenotypes provide a framework for future studies of TLR4 signaling, as the interaction supported by each critical surface residue will need to be defined.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.