ArticleCell death and differentiation2021
Cell fate determined by the activation balance between PKR and SPHK1.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
The trial behind it
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- STK39 promotes the evolution cascade of hepatocellular carcinoma by facilitating PKR/NF-κB-mediated macrophage inflammatory response.Oncogene · 2026Article
- Time- and Dose-Dependent PSP-Induced Modulation of Antiviral Signaling Networks in CD4+ T Cells.International journal of molecular sciences · 2026Article
- Sphingolipid Metabolism in the Pathogenesis of Hashimoto's Thyroiditis.International journal of molecular sciences · 2025Review
- OTUB1 antagonizes TRIM21 to induce deubiquitination of SPHK1 and promote the progression of hepatocellular carcinoma.Oncogene · 2025Article
- Transcriptional signature of rapidly responding NK cells reveals S1P5 and CXCR4 as anti-tumor response disruptors.Scientific reports · 2025Article
- MSCs Suppress Macrophage Necroptosis and Foster Liver Regeneration by Modulating SP1/SK1 Axis in Treating Acute Severe Autoimmune Hepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Sphingolipids modulate redox signalling during human sperm capacitation.Human reproduction (Oxford, England) · 2025Article
- Activation of PKR by a short-hairpin RNA.Scientific reports · 2024Article
- Activation of PKR by a short-hairpin RNA.bioRxiv : the preprint server for biology · 2024Article
- Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?International journal of molecular sciences · 2023Review
- Regulation of PKR-dependent RNA translation inhibition by TRIM21 upon virus infection or other stress.PLoS pathogens · 2023Article
- The Role and Therapeutic Potential of the Integrated Stress Response in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
- Hemorrhage-Induced Sphingosine Kinase 1 Contributes to Ferroptosis-Mediated Secondary Brain Injury in Intracerebral Hemorrhage.Molecular neurobiology · 2022Article
- Divergence of Intracellular Trafficking of Sphingosine Kinase 1 and Sphingosine-1-Phosphate Receptor 3 in MCF-7 Breast Cancer Cells and MCF-7-Derived Stem Cell-Enriched Mammospheres.International journal of molecular sciences · 2021Article
- Review
- The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration.Frontiers in aging neuroscience · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) activation via autophosphorylation is the central cellular response to stress that promotes cell death or apoptosis. However, the key factors and mechanisms behind the simultaneous activation of pro-survival signaling pathways remain unknown. We have discovered a novel regulatory mechanism for the maintenance of cellular homeostasis that relies on the phosphorylation interplay between sphingosine kinase 1 (SPHK1) and PKR during exogenous stress. We identified SPHK1 as a previously unrecognized PKR substrate. Phosphorylated SPHK1, a central kinase, mediates the activation of PKR-induced pro-survival pathways by the S1P/S1PR1/MAPKs/IKKα signal axis, and antagonizes PKR-mediated endoplasmic reticulum (ER) stress signal transduction under stress conditions. Otherwise, phosphorylated SPHK1 also acts as the negative feedback factor, preferentially binding to the latent form of PKR at the C-terminal kinase motif, inhibiting the homodimerization of PKR, suppressing PKR autophosphorylation, and reducing the signaling strength for cell death and apoptosis. Our results suggest that the balance of the activation levels between PKR and SPHK1, a probable hallmark of homeostasis maintenance, determines cell fate during cellular stress response.
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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.