ArticleThe Journal of biological chemistry2014
Tumor progression locus 2-dependent oxidative burst drives phosphorylation of extracellular signal-regulated kinase during TLR3 and 9 signaling.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- NLRP3 inflammasomes at the ARDS-cancer interface: mechanisms and translational hypotheses.Frontiers in immunology · 2026Review
- Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens.Biochemistry and biophysics reports · 2025Article
- TLR agonists as adjuvants for viral vaccines: mechanisms, applications, and future directions.Frontiers in microbiology · 2025Review
- TPL2 Promotes Gastric Cancer Progression and Chemoresistance Through a Hypoxia-Induced Positive Feedback Loop with PPARδ.International journal of biological sciences · 2025Article
- Enhanced transgene expression from single-stranded AAV vectors in human cellsMolecular therapy. Nucleic acids · 2024Article
- Influenza-induced Tpl2 expression within alveolar epithelial cells is dispensable for host viral control and anti-viral immunity.PloS one · 2022Article
- NETosis as a Pathogenic Factor for Heart Failure.Oxidative medicine and cellular longevity · 2021Review
- HSV-1/TLR9-Mediated IFNβ and TNFα Induction Is Mal-Dependent in Macrophages.Journal of innate immunity · 2020Article
- Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity.Theranostics · 2020Review
- Flow-induced mechanotransduction in skeletal cells.Biophysical reviews · 2019Review
- Recognition of early and late stages of bladder cancer using metabolites and machine learning.Metabolomics : Official journal of the Metabolomic Society · 2019Article
- Tpl2 Promotes Innate Cell Recruitment and Effector T Cell Differentiation To Limit Citrobacter rodentium Burden and Dissemination.Infection and immunity · 2017Article
- Severe Dermatitis Associated with SpontaneousComparative medicine · 2017Article
- Tpl2 promotes neutrophil trafficking, oxidative burst, and bacterial killing.Journal of leukocyte biology · 2017Article
- Double-stranded RNA upregulates the expression of inflammatory mediators in human aortic valve cells through the TLR3-TRIF-noncanonical NF-κB pathway.American journal of physiology. Cell physiology · 2017Article
- Downregulation of vimentin in macrophages infected with live Mycobacterium tuberculosis is mediated by Reactive Oxygen Species.Scientific reports · 2016Article
- Tumor Progression Locus 2 Promotes Induction of IFNλ, Interferon Stimulated Genes and Antigen-Specific CD8+ T Cell Responses and Protects against Influenza Virus.PLoS pathogens · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal transduction via NFκB and MAP kinase cascades is a universal response initiated upon pathogen recognition by Toll-like receptors (TLRs). How activation of these divergent signaling pathways is integrated to dictate distinct immune responses to diverse pathogens is still incompletely understood. Herein, contrary to current perception, we demonstrate that a signaling pathway defined by the inhibitor of κB kinase β (IKKβ), MAP3 kinase tumor progression locus 2 (Tpl2/MAP3K8), and MAP kinase ERK is differentially activated by TLRs. TLRs 2, 4, and 7 directly activate this inflammatory axis, inducing immediate ERK phosphorylation and early TNFα secretion. In addition to TLR adaptor proteins, IKKβ-Tpl2-ERK activation by TLR4 is regulated by the TLR4 co-receptor CD14 and the tyrosine kinase Syk. Signals from TLRs 3 and 9 do not initiate early activation of IKKβ-Tpl2-ERK pathway but instead induce delayed, NADPH-oxidase-dependent ERK phosphorylation and TNFα secretion via autocrine reactive oxygen species signaling. Unexpectedly, Tpl2 is an essential regulator of ROS production during TLR signaling. Overall, our study reveals distinct mechanisms activating a common inflammatory signaling cascade and delineates differences in MyD88-dependent signaling between endosomal TLRs 7 and 9. These findings further confirm the importance of Tpl2 in innate host defense mechanisms and also enhance our understanding of how the immune system tailors pathogen-specific gene expression patterns.
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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.