ArticleThe Journal of biological chemistry2012
Phospholipase Cγ-2 and intracellular calcium are required for lipopolysaccharide-induced Toll-like receptor 4 (TLR4) endocytosis and interferon regulatory factor 3 (IRF3) activation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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.
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Who cites it
77 citing papers in PubMed, 124 citations in OpenAlex.
- PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain.bioRxiv : the preprint server for biology · 2026Article
- Diacylglycerol kinase-ε is required for the formation of GPI-anchored CD14 and the LPS-induced proinflammatory responses of macrophages.Cell communication and signaling : CCS · 2026Article
- Harnessing stem cell therapeutics in LPS-induced animal models: mechanisms, efficacies, and future directions.Stem cell research & therapy · 2025Review
- An examination of the LPS-TLR4 immune response through the analysis of molecular structures and protein-protein interactions.Cell communication and signaling : CCS · 2025Review
- PLCG2, A Regulator of Lung Adenocarcinoma Proliferation and Migration Associated with Immune Infiltration.Current cancer drug targets · 2025Article
- Role and mechanism of gut microbiota in regulating interferon-mediated programmed cell death in colorectal cancer.Frontiers in immunology · 2025Review
- Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.Medicinal research reviews · 2024Review
- Tropomodulin1 exacerbates inflammatory response in macrophages by negatively regulating LPS-induced TLR4 endocytosis.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- Microglial modulation as a therapeutic strategy in Alzheimer's disease: Focus on microglial preconditioning approaches.Journal of cellular and molecular medicine · 2024Review
- LPS exacerbates TRPV4-mediated itch through the intracellular TLR4-PI3K signalling.Journal of cellular and molecular medicine · 2024Article
- Crosstalk between P2Y receptors and cyclooxygenase activity in inflammation and tissue repair.Purinergic signalling · 2024Review
- Calcium Signalling in Microglia.Advances in neurobiology · 2024Review
- Resistin Induces Migration and Invasion in PC3 Prostate Cancer Cells: Role of Extracellular Vesicles.Life (Basel, Switzerland) · 2023Article
- Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway.Lipids in health and disease · 2023Article
- P2Y2 purinergic receptor gene deletion protects mice from bacterial endotoxin and sepsis-associated liver injury and mortality.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Article
- Carriers of the p.P522R variant in PLCγ2 have a slightly more responsive immune system.Molecular neurodegeneration · 2023Article
- The Role of Phospholipase Activity of Peroxiredoxin 6 in Its Transmembrane Transport and Protective Properties.International journal of molecular sciences · 2022Article
- TRPC channels blockade abolishes endotoxemic cardiac dysfunction by hampering intracellular inflammation and CaNature communications · 2022Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Toll-like receptor 4 (TLR4) is unique among the TLRs in its use of multiple adaptor proteins leading to activation of both the interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) pathways. Previous work has demonstrated that TLR4 initiates NF-κB activation from the plasma membrane, but that subsequent TLR4 translocation to the endosomes is required for IRF3 activation. Here we have characterized several components of the signaling pathway that governs TLR4 translocation and subsequent IRF3 activation. We find that phospholipase C γ2 (PLCγ2) accounts for LPS-induced inositol 1,4,5-trisphosphate (IP(3)) production and subsequent calcium (Ca(2+)) release. Blockage of PLCγ2 function by inhibitors or knockdown of PLCγ2 expression by siRNAs in RAW 264.7 macrophages lead to reduced IRF3, but enhanced NF-κB activation. In addition, bone marrow-derived macrophages from PLCγ2-deficient mice showed impaired IRF3 phosphorylation and expression of IRF3-regulated genes after LPS stimulation. Using cell fractionation, we show that PLCγ2-IP(3)-Ca(2+) signaling cascade is required for TLR4 endocytosis following LPS stimulation. In conclusion, our results describe a novel role of the PLCγ2-IP(3)-Ca(2+) cascade in the LPS-induced innate immune response pathway where release of intracellular Ca(2+) mediates TLR4 trafficking and subsequent activation of IRF3.
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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 OpenQuestion graph.