ArticleCell2010
Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis.
Article in Cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 253 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.
The trial behind it
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
253 citing papers in PubMed, 1 synthesis or guideline pooled it, 498 citations in OpenAlex.
- -308G/A polymorphism of tumor necrosis factor alpha (TNF-α) gene and metabolic syndrome susceptibility: a meta-analysis.Scientific reports · 2021Pooled it
- Ursodeoxycholic acid: Effects on hepatic unfolded protein response, apoptosis and oxidative stress in morbidly obese patients.Liver international : official journal of the International Association for the Study of the Liver · 2018Trial
- Excessive EFHD1-dependent ER-mitochondrial contacts drive a maladaptive antiviral response in metabolic liver disease.The Journal of clinical investigation · 2026Article
- Long-term imoxin treatment does not attenuate disease severity in dystrophic diaphragm of male mice.Physiological reports · 2026Article
- Targeting the epigenome and the integrated stress response to normalize colorectal cancer subclonal plasticity and progression.Cell death & disease · 2026Article
- Lactic acid drives NLRP3 inflammasome activation and caspase-1-like cytokine cleavage via intracellular acidification.Cell death & disease · 2026Article
- CAV2 Modulates Cetuximab Sensitivity in HNSCC via Ubiquitin-Mediated Disruption of the PACT-PKR Axis.Cancers · 2026Article
- PPARα-NF-κB heterodimer mediates obesity-induced diastolic dysfunction through autocrine production of IL-6.The Journal of clinical investigation · 2026Article
- Excessive CabioRxiv : the preprint server for biology · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- Obesity-induced NLRP3 inflammasome activation in nucleus pulposus cells accelerates intervertebral disk degeneration.Journal of orthopaedic surgery and research · 2025Article
- Essential role of protein kinase R in the pathogenesis of pulmonary veno-occlusive disease.JCI insight · 2025Article
- The dsRNA-dependent kinase (PKR) inhibits the growth ofParasitology · 2025Article
- Role of mouse adenovirus type 1 E4orf6-induced degradation of protein kinase R in pathogenesis.Journal of virology · 2025Article
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- PKR Inhibition Prevents Neuroinflammation and Rescues Depressive-Like Behaviors via BDNF/TrkB Signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- PKR modulates sterile systemic inflammation-triggered neuroinflammation and brain glucose metabolism disturbances.Frontiers in immunology · 2025Article
- The Integrated Stress Response in Pancreatic Development, Tissue Homeostasis, and Cancer.Gastroenterology · 2024Review
- Endoplasmic reticulum stress in diseases.MedComm · 2024Review
193 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
As chronic inflammation is a hallmark of obesity, pathways that integrate nutrient- and pathogen sensing pathways are of great interest in understanding the mechanisms of insulin resistance, type 2 diabetes, and other chronic metabolic pathologies. Here, we provide evidence that double-stranded RNA-dependent protein kinase (PKR) can respond to nutrient signals as well as endoplasmic reticulum (ER) stress and coordinate the activity of other critical inflammatory kinases such as the c-Jun N-terminal kinase (JNK) to regulate insulin action and metabolism. PKR also directly targets and modifies insulin receptor substrate and hence integrates nutrients and insulin action with a defined pathogen response system. Dietary and genetic obesity features marked activation of PKR in adipose and liver tissues and absence of PKR alleviates metabolic deterioration due to nutrient or energy excess in mice. These findings demonstrate PKR as a critical component of an inflammatory complex that responds to nutrients and organelle dysfunction.
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What OpenQuestion holds
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.