ArticlePloS one2012
DOK3 negatively regulates LPS responses and endotoxin tolerance.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 37 citations in OpenAlex.
- Dissection of MAPK and NF-κB p65 signaling dynamics underlying LPS tolerance in macrophages at the single-cell level.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Augmentation of PRDX1-DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation.Acta pharmaceutica Sinica. B · 2025Article
- The Abca7Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Adaptor molecules mediate negative regulation of macrophage inflammatory pathways: a closer look.Frontiers in immunology · 2024Review
- Molecular Characterization, Expression, and Regulatory Signal Pathway Analysis of Inflammasome Component Apoptosis-Associated Speck-like Protein Containing a CARD Domain (ASC) in Large Yellow Croaker (International journal of molecular sciences · 2023Article
- Dok3 restrains neutrophil production of calprotectin during TLR4 sensing of SARS-CoV-2 spike protein.Frontiers in immunology · 2022Article
- Shaping the Innate Immune Response Through Post-Transcriptional Regulation of Gene Expression Mediated by RNA-Binding Proteins.Frontiers in immunology · 2021Review
- TLR4 abrogates the Th1 immune response through IRF1 and IFN-β to prevent immunopathology during L. infantum infection.PLoS pathogens · 2020Article
- Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide-induced acute pneumonia in mice.Journal of cellular and molecular medicine · 2020Article
- Emerging Roles of Downstream of Kinase 3 in Cell Signaling.Frontiers in immunology · 2020Review
- Dok-3 deficient mice display different immune clustering and Tim-3 expression.European journal of medical research · 2019Article
- Dok3-protein phosphatase 1 interaction attenuates Card9 signaling and neutrophil-dependent antifungal immunity.The Journal of clinical investigation · 2019Article
- MALDI-TOF MS monitoring of PBMC activation status in sepsis.BMC infectious diseases · 2018Article
- DOK3 Modulates Bone Remodeling by Negatively Regulating Osteoclastogenesis and Positively Regulating Osteoblastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- A functional genomics predictive network model identifies regulators of inflammatory bowel disease.Nature genetics · 2017Article
- MicroRNA-124 negatively regulates LPS-induced TNF-α production in mouse macrophages by decreasing protein stability.Acta pharmacologica Sinica · 2016Article
- SMAD4 is Involved in the Development of Endotoxin Tolerance in Microglia.Cellular and molecular neurobiology · 2016Article
- Epigenetic Regulation of Tolerance to Toll-Like Receptor Ligands in Alveolar Epithelial Cells.American journal of respiratory cell and molecular biology · 2015Article
- Mice lacking α1,3-fucosyltransferase 9 exhibit modulation of in vivo immune responses against pathogens.Pathology international · 2014Article
- The effects of Twist-2 on liver endotoxin tolerance induced by a low dose of lipopolysaccharide.Inflammation · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Innate immune activation via Toll-like receptors (TLRs), although critical for host defense against infection, must be regulated to prevent sustained cell activation that can lead to cell death. Cells repeatedly stimulated with lipopolysaccharide (LPS) develop endotoxin tolerance making the cells hypo-responsive to additional TLR stimulation. We show here that DOK3 is a negative regulator of TLR signaling by limiting LPS-induced ERK activation and cytokine responses in macrophages. LPS induces ubiquitin-mediated degradation of DOK3 leading to SOS1 degradation and inhibition of ERK activation. DOK3 mice are hypersensitive to sublethal doses of LPS and have altered cytokine responses in vivo. During endotoxin tolerance, DOK3 expression remains stable, and it negatively regulates the expression of SHIP1, IRAK-M, SOCS1, and SOS1. As such, DOK3-deficient macrophages are more sensitive to LPS-induced tolerance becoming tolerant at lower levels of LPS than wild type cells. Taken together, the absence of DOK3 increases LPS signaling, contributing to LPS-induced tolerance. Thus, DOK3 plays a role in TLR signaling during both naïve and endotoxin-induced tolerant conditions.
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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.