ArticleThe Journal of biological chemistry2014
Activation of protein kinase PKR requires dimerization-induced cis-phosphorylation within the activation loop.
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 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- Akabane virus reprograms the PKR‑eIF2α‑SGs/PBs axis to fine-tune cap-snatching efficiency.Virulence · 2026Article
- Regulatory mechanism of heme-regulated inhibitor through autophosphorylation-driven activation and heme-induced deactivation.Journal of biochemistry · 2026Article
- Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity.Nature communications · 2026Article
- Phosphoproteomics Data-Driven Integrative Analysis of Autophosphorylation Sites in the Human Kinome.International journal of molecular sciences · 2026Article
- Cardiovirus-Mediated PKR inhibition results from nucleocytoplasmic trafficking disruption.PLoS pathogens · 2025Article
- Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review.Molecular biology reports · 2025Review
- Cryo-EM structure of histidyl-tRNA synthetase-like domain reveals activating crossed helices at the core of GCN2.PNAS nexus · 2024Article
- ADAR1 could be a potential diagnostic target for intrauterine infection patients.Scientific reports · 2024Article
- Activation of PKR by a short-hairpin RNA.Scientific reports · 2024Article
- Dimerization Promotes PKR Activation by Modulating Energetics of αC Helix Conversion between Active and Inactive Conformations.The journal of physical chemistry. B · 2024Article
- Activation of PKR by a short-hairpin RNA.bioRxiv : the preprint server for biology · 2024Article
- ADAR Family Proteins: A Structural Review.Current issues in molecular biology · 2024Review
- RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024Review
- A critical evaluation of protein kinase regulation by activation loop autophosphorylation.eLife · 2023Article
- Discovery and identification of EIF2AK2 as a direct key target of berberine for anti-inflammatory effects.Acta pharmaceutica Sinica. B · 2023Article
- ADAR1 has an oncogenic function and can be a prognostic factor in cervical cancer.Scientific reports · 2023Article
- Crocodilepox Virus Protein 157 Is an Independently Evolved Inhibitor of Protein Kinase R.Viruses · 2022Article
- Cellular origins of dsRNA, their recognition and consequences.Nature reviews. Molecular cell biology · 2022Review
- Temporal control of the integrated stress response by a stochastic molecular switch.Science advances · 2022Article
- Battle Royale: Innate Recognition of Poxviruses and Viral Immune Evasion.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase R (PKR) functions in a plethora of cellular processes, including viral and cellular stress responses, by phosphorylating the translation initiation factor eIF2α. The minimum requirements for PKR function are homodimerization of its kinase and RNA-binding domains, and autophosphorylation at the residue Thr-446 in a flexible loop called the activation loop. We investigated the interdependence between dimerization and Thr-446 autophosphorylation using the yeast Saccharomyces cerevisiae model system. We showed that an engineered PKR that bypassed the need for Thr-446 autophosphorylation (PKR(T446∼P)-bypass mutant) could function without a key residue (Asp-266 or Tyr-323) that is essential for PKR dimerization, suggesting that dimerization precedes and stimulates activation loop autophosphorylation. We also showed that the PKR(T446∼P)-bypass mutant was able to phosphorylate eIF2α even without its RNA-binding domains. These two significant findings reveal that PKR dimerization and activation loop autophosphorylation are mutually exclusive yet interdependent processes. Also, we provide evidence that Thr-446 autophosphorylation during PKR activation occurs in a cis mechanism following dimerization.
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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.