ArticleJournal of proteome research2014
Phosphoproteome profiling of the macrophage response to different toll-like receptor ligands identifies differences in global phosphorylation dynamics.
Article in Journal of proteome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective.Experimental & molecular medicine · 2024Pooled it
- Quantitative Modeling of TLR Signaling Reveals Missing Negative Feedback Guiding Identification of TANK-IKKε Checkpoint.bioRxiv : the preprint server for biology · 2026Article
- Article
- Phosphoproteomics in Vascular Biology and Disease: Illuminating Signaling in the Vessel.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Structural diversity of lipid A modulates neutrophil proteome and secretome responses.Journal of proteomics · 2026Article
- Host-directed therapeutics against antimicrobial-resistant bacterial infections: emerging roles of multi-omics and systems biology.Frontiers in pharmacology · 2026Review
- Phosphoproteomic profiling of lipopolysaccharide stimulated toll-like receptor pathways in macrophages.Scientific data · 2025Article
- A Phosphoproteomic Analysis of Mycobacterial PknG-Mediated Host Immune Evasion.Journal of proteome research · 2025Article
- Phosphoproteomic Profiling Reveals mTOR Signaling in Sustaining Macrophage Phagocytosis of Cancer Cells.Cancers · 2024Article
- Lipopolysaccharide Regulates the Macrophage RNA-Binding Proteome.Journal of proteome research · 2024Article
- Phosphorylation of PFKL regulates metabolic reprogramming in macrophages following pattern recognition receptor activation.Nature communications · 2024Article
- Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome.Nature communications · 2024Article
- Myristoylated, alanine-rich C-kinase substrate (MARCKS) regulates toll-like receptor 4 signaling in macrophages.Scientific reports · 2023Article
- Omics and systems view of innate immune pathways.Proteomics · 2023Review
- Absolute protein quantitation of the mouse macrophage Toll-like receptor and chemotaxis pathways.Scientific data · 2022Article
- Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors.Cell reports · 2021Article
- Harnessing the Potential of Multiomics Studies for Precision Medicine in Infectious Disease.Open forum infectious diseases · 2021Review
- Dynamic ADP-Ribosylome, Phosphoproteome, and Interactome in LPS-Activated Macrophages.Journal of proteome research · 2020Article
- Phosphoproteome Analysis in Immune Cell Signaling.Current protocols in immunology · 2020Article
- The DNA Sensor cGAS is Decorated by Acetylation and Phosphorylation Modifications in the Context of Immune Signaling.Molecular & cellular proteomics : MCP · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Toll-like receptors (TLRs) are among the first sensors that detect infection and drive immune response. Macrophages encountering a pathogen are usually stimulated not by one TLR, but by a combination of TLRs engaged by distinct microbe ligands. To understand the integrated signaling under complex conditions, we investigated the differences in the phosphoprotein signaling cascades triggered by TLR2, TLR4, and TLR7 ligands using a single responding cell population. We performed a global, quantitative, early poststimulation kinetic analysis of the mouse macrophage phosphoproteome using stable isotope labeling with amino acids coupled to phosphopeptide enrichment and high-resolution mass spectrometry. For each TLR ligand, we found marked elevation of phosphorylation of cytoskeleton components, GTPases of the Rho family, and phospholipase C signaling pathway proteins. Phosphorylation of proteins involved in phagocytosis was only seen in response to TLR2 and TLR4 but not to TLR7 activation. Changes in the phosphorylation of proteins involved in endocytosis were delayed in response to TLR2 as compared to TLR4 ligands. These findings reveal that the phosphoproteomic response to stimulation of distinct TLRs varies both in the major modification targets and the phosphorylation dynamics. These results advance the understanding of how macrophages sense and respond to a diverse set of TLR stimuli.
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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.