ArticleMolecular biology of the cell2017
Association of Lyn kinase with membrane rafts determines its negative influence on LPS-induced signaling.
Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed.
- Palmitoylation-dependent regulation of innate and adaptive immunity: molecular insights and translational opportunities.Cellular & molecular biology letters · 2026Review
- Lyn expression in macrophages promotes TLR activation and restricts proliferation in an isoform-independent manner.Journal of leukocyte biology · 2025Article
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- Exploring the role of palmitoylation in sepsis: mechanistic insights and future perspectives.Molecular medicine (Cambridge, Mass.) · 2025Review
- Review
- Protein palmitoylation: an emerging regulator of inflammatory signaling and diseases.Frontiers in immunology · 2025Review
- Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14.Cellular and molecular life sciences : CMLS · 2024Article
- Sorafenib inhibits LPS-induced inflammation by regulating Lyn-MAPK-NF-kB/AP-1 pathway and TLR4 expression.Cell death discovery · 2022Article
- Review
- Palm Oil-Rich Diet Affects Murine Liver Proteome andInternational journal of molecular sciences · 2021Article
- Inhibitory affinity modulation of FcγRIIA ligand binding by glycosphingolipids by inside-out signaling.Cell reports · 2021Article
- TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.Cellular and molecular life sciences : CMLS · 2021Review
- Function of Protein S-Palmitoylation in Immunity and Immune-Related Diseases.Frontiers in immunology · 2021Review
- Loci Associated With Antibody Response in Feral Swine (Frontiers in veterinary science · 2020Article
- Protein Palmitoylation in Leukocyte Signaling and Function.Frontiers in cell and developmental biology · 2020Review
- Role of Membrane Cholesterol Levels in Activation of Lyn upon Cell Detachment.International journal of molecular sciences · 2018Review
- Lipopolysaccharide Upregulates Palmitoylated Enzymes of the Phosphatidylinositol Cycle: An Insight from Proteomic Studies.Molecular & cellular proteomics : MCP · 2018Article
- Src family kinase tyrosine phosphorylates Toll-like receptor 4 to dissociate MyD88 and Mal/Tirap, suppressing LPS-induced inflammatory responses.Biochemical pharmacology · 2018Article
- Protein Palmitoylation and Its Role in Bacterial and Viral Infections.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipopolysaccharide (LPS) is the component of Gram-negative bacteria that activates Toll-like receptor 4 (TLR4) to trigger proinflammatory responses. We examined the involvement of Lyn tyrosine kinase in TLR4 signaling of macrophages, distinguishing its catalytic activity and intermolecular interactions. For this, a series of Lyn-GFP constructs bearing point mutations in particular domains of Lyn were overexpressed in RAW264 macrophage-like cells or murine peritoneal macrophages, and their influence on LPS-induced responses was analyzed. Overproduction of wild-type or constitutively active Lyn inhibited production of TNF-α and CCL5/RANTES cytokines and down-regulated the activity of NFκB and IRF3 transcription factors in RAW264 cells. The negative influence of Lyn was nullified by point mutations of Lyn catalytic domain or Src homology 2 (SH2) or SH3 domains or of the cysteine residue that undergoes LPS-induced palmitoylation. Depending on the cell type, overproduction of those mutant forms of Lyn could even up-regulate LPS-induced responses, and this effect was reproduced by silencing of endogenous Lyn expression. Simultaneously, the Lyn mutations blocked its LPS-induced accumulation in the raft fraction of RAW264 cells. These data indicate that palmitoylation, SH2- and SH3-mediated intermolecular interactions, and the catalytic activity of Lyn are required for its accumulation in rafts, thereby determining the negative regulation of TLR4 signaling.
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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 Socratic graph.