ArticleMolecular biology of the cell2010
The double-stranded RNA-dependent protein kinase differentially regulates insulin receptor substrates 1 and 2 in HepG2 cells.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 46 citations in OpenAlex.
- Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.Biomolecules · 2026Review
- The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.The Journal of endocrinology · 2024Review
- Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease.International journal of biological sciences · 2023Review
- Kinases on Double Duty: A Review of UniProtKB Annotated Bifunctionality within the Kinome.Biomolecules · 2022Review
- Roles of Ceramides in Non-Alcoholic Fatty Liver Disease.Journal of clinical medicine · 2021Review
- Def6 regulates endogenous type-I interferon responses in osteoblasts and suppresses osteogenesis.eLife · 2020Article
- Kinome Profiling Reveals Abnormal Activity of Kinases in Skeletal Muscle From Adults With Obesity and Insulin Resistance.The Journal of clinical endocrinology and metabolism · 2020Article
- Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases.International journal of molecular sciences · 2020Review
- Catestatin improves insulin sensitivity by attenuating endoplasmic reticulum stress:Computational and structural biotechnology journal · 2020Article
- Bone protection by inhibition of microRNA-182.Nature communications · 2018Article
- Sustained Action of Ceramide on the Insulin Signaling Pathway in Muscle Cells: IMPLICATION OF THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE.The Journal of biological chemistry · 2016Article
- Cytoplasmic RNA Granules and Viral Infection.Annual review of virology · 2014Article
- Role of interferon alpha in endothelial dysfunction: insights into endothelial nitric oxide synthase-related mechanisms.The American journal of the medical sciences · 2014Review
- PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator.Genes & development · 2014Article
- Oxidative stress-associated protein tyrosine kinases and phosphatases in Fanconi anemia.Antioxidants & redox signaling · 2014Review
- Review
- Development of novel cell lines of diabetic dysfunction model fit for cell-based screening tests of medicinal materials.Cytotechnology · 2013Article
- dsRNA-dependent protein kinase PKR and its role in stress, signaling and HCV infection.Viruses · 2012Review
- Fanconi anemia links reactive oxygen species to insulin resistance and obesity.Antioxidants & redox signaling · 2012Article
- Synergy analysis reveals association between insulin signaling and desmoplakin expression in palmitate treated HepG2 cells.PloS one · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Initially identified to be activated upon virus infection, the double-stranded RNA-dependent protein kinase (PKR) is best known for triggering cell defense responses by phosphorylating eIF-2α, thus suppressing RNA translation. We as well as others showed that the phosphorylation of PKR is down-regulated by insulin. In the present study, we further uncovered a novel function of PKR in regulating the IRS proteins. We found that PKR up-regulates the inhibitory phosphorylation of IRS1 at Ser312, which suppresses the tyrosine phosphorylation of IRS1. This effect of PKR on the phosphorylation of IRS1 is mediated by two other protein kinases, JNK and IKK. In contrast, PKR regulates IRS2, another major IRS family protein in the liver, at the transcriptional rather than the posttranslational level, and this effect is mediated by the transcription factor, FoxO1, which has been previously shown to be regulated by insulin and plays a significant role in glucose homeostasis and energy metabolism. In summary, we found for the first time that initially known as a virus infection response gene, PKR regulates the upstream central transmitters of insulin signaling, IRS1 and IRS2, through different mechanisms.
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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.