ArticleScientific reports2021
PKR activity modulation by phosphomimetic mutations of serine residues located three aminoacids upstream of double-stranded RNA binding motifs.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 48 citations in OpenAlex.
- Tripartite motif-containing 34 (TRIM34) protein interacts with the nucleocytoplasmic transport machinery and negatively modulates antiviral responses.PLoS pathogens · 2026Article
- Cardiovirus-Mediated PKR inhibition results from nucleocytoplasmic trafficking disruption.PLoS pathogens · 2025Article
- Review
- The leader proteins of Theiler's virus and Boone cardiovirus use a combination of short linear motifs (SLiMs) to target RSK kinases to the nuclear pore complex.Journal of virology · 2025Article
- A simple workflow to identify novel small linear motif (SLiM)-mediated interactions with AlphaFold.Briefings in bioinformatics · 2025Article
- Orientia tsutsugamushi modulates p53, the cell cycle, and genotoxicity to maintain its intracellular niche.Nature communications · 2025Article
- Crystal structures of the phosphorylation mimics of human cytosolic branched chain aminotransferase.Archives of biochemistry and biophysics · 2025Article
- IFN alpha inducible protein 27 (IFI27) acts as a positive regulator of PACT-dependent PKR activation after RNA virus infections.PLoS pathogens · 2025Article
- The "DDVF" motif used by viral and bacterial proteins to hijack RSK kinases mimics a short linear motif (SLiM) found in proteins related to the RAS-ERK MAP kinase pathway.PLoS pathogens · 2025Article
- Dysregulated RNA editing of EIF2AK2 in polycystic ovary syndrome: clinical relevance and functional implications.BMC medicine · 2024Article
- The use of RNA-based treatments in the field of cancer immunotherapy.Molecular cancer · 2023Review
- Mechanisms of circular RNA degradation.Communications biology · 2022Review
- Move and countermove: the integrated stress response in picorna- and coronavirus-infected cells.Current opinion in immunology · 2022Review
- Systematic comparison of differential expression networks in MTB mono-, HIV mono- and MTB/HIV co-infections for drug repurposing.PLoS computational biology · 2022Article
- Cardiovirus leader proteins retarget RSK kinases toward alternative substrates to perturb nucleocytoplasmic traffic.PLoS pathogens · 2022Article
- Inhibition of PKR by Viruses.Frontiers in microbiology · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2), better known as PKR, plays a key role in the response to viral infections and cellular homeostasis by regulating mRNA translation. Upon binding dsRNA, PKR is activated through homodimerization and subsequent autophosphorylation on residues Thr446 and Thr451. In this study, we identified a novel PKR phosphorylation site, Ser6, located 3 amino acids upstream of the first double-stranded RNA binding motif (DRBM1). Another Ser residue occurs in PKR at position 97, the very same position relative to the DRBM2. Ser or Thr residues also occur 3 amino acids upstream DRBMs of other proteins such as ADAR1 or DICER. Phosphoinhibiting mutations (Ser-to-Ala) introduced at Ser6 and Ser97 spontaneously activated PKR. In contrast, phosphomimetic mutations (Ser-to-Asp) inhibited PKR activation following either poly (I:C) transfection or virus infection. These mutations moderately affected dsRNA binding or dimerization, suggesting a model where negative charges occurring at position 6 and 97 tighten the interaction of DRBMs with the kinase domain, thus keeping PKR in an inactive closed conformation even in the presence of dsRNA. This study provides new insights on PKR regulation mechanisms and identifies Ser6 and Ser97 as potential targets to modulate PKR activity for therapeutic purposes.
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