ArticleEuropean journal of immunology2023
TLR4 phosphorylation at tyrosine 672 activates the ERK/c-FOS signaling module for LPS-induced cytokine responses in macrophages.
Article in European journal of immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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.
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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.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Dissecting temporal regulation of the TLR4-IL-6 axis using systematic targeted inhibition.Scientific reports · 2026Article
- A Novel Tyrosine Kinase Axis in Innate Immune Signaling.Viruses · 2025Review
- Cardiolipin inhibits the non-canonical inflammasome by preventing LPS binding to caspase-4/11.The EMBO journal · 2025Article
- HMGB1 Regulates Adipocyte Lipolysis via Caveolin-1 Signaling: Implications for Metabolic and Cardiovascular Diseases.International journal of molecular sciences · 2025Article
- Article
- Acetylation of TIR domains in the TLR4-Mal-MyD88 complex regulates immune responses in sepsis.The EMBO journal · 2024Article
- Protective effects of flavonoids against intracerebral and subarachnoid hemorrhage (Review).Experimental and therapeutic medicine · 2024Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
Abstract
TLRs engage numerous adaptor proteins and signaling molecules, enabling a complex series of post-translational modifications (PTMs) to mount inflammatory responses. TLRs themselves are post-translationally modified following ligand-induced activation, with this being required to relay the full spectrum of proinflammatory signaling responses. Here, we reveal indispensable roles for TLR4 Y672 and Y749 phosphorylation in mounting optimal LPS-inducible inflammatory responses in primary mouse macrophages. LPS promotes phosphorylation at both tyrosine residues, with Y749 phosphorylation being required for maintenance of total TLR4 protein levels and Y672 phosphorylation exerting its pro-inflammatory effects more selectively by initiating ERK1/2 and c-FOS phosphorylation. Our data also support a role for the TLR4-interacting membrane proteins SCIMP and the SYK kinase axis in mediating TLR4 Y672 phosphorylation to permit downstream inflammatory responses in murine macrophages. The corresponding residue in human TLR4 (Y674) is also required for optimal LPS signaling responses. Our study, thus, reveals how a single PTM on one of the most widely studied innate immune receptors orchestrates downstream inflammatory responses.
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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.