ArticleMolecular and cellular biology2000
PKR stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 225 citations in OpenAlex.
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Long-term imoxin treatment does not attenuate disease severity in dystrophic diaphragm of male mice.Physiological reports · 2026Article
- DHX36 is a regulatory switch in the interferon-mediated antiviral response.Science advances · 2026Article
- Disruptions of cell signaling pathways in myotonic dystrophy type 1 skeletal muscle, their pathogenic impact, and potential for combinatorial therapeutics.The Journal of biological chemistry · 2026Review
- Roles of the integrated stress response in regulation of inflammatory reactions.Frontiers in immunology · 2026Review
- Review
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- PACT suppresses PKR activation through dsRNA binding and dimerization, and is a therapeutic target for triple-negative breast cancer.RNA (New York, N.Y.) · 2025Article
- Poxvirus K3 Orthologs Regulate NF-κB-Dependent Inflammatory Responses by Targeting the PKR-eIF2α Axis in Multiple Species.Vaccines · 2025Article
- The dsRNA-dependent kinase (PKR) inhibits the growth ofParasitology · 2025Article
- Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review.Molecular biology reports · 2025Review
- PKR associates with 4.1R to promote anchorage-independent growth of hepatocellular carcinoma and lead to poor prognosis.Scientific reports · 2024Article
- Sleep-wake behavior and responses to sleep deprivation and immune challenge of protein kinase RNA-activated knockout mice.Brain, behavior, and immunity · 2024Article
- Activation of protein kinase receptor (PKR) plays a pro-viral role in mammarenavirus-infected cells.Journal of virology · 2024Article
- The helicase domain of human Dicer prevents RNAi-independent activation of antiviral and inflammatory pathways.The EMBO journal · 2024Article
- E3 ligase HECTD3 promotes RNA virus replication and virus-induced inflammation via K33-linked polyubiquitination of PKR.Cell death & disease · 2023Article
- Differential protein expression in endothelial cells exposed to serum from patients with acute graft-vs-host disease, depending on steroid response.Journal of cellular and molecular medicine · 2023Article
- Role of mitochondrial stress and the NLRP3 inflammasome in lung diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Smooth Muscle Cell Phenotypic Switch Induced by Traditional Cigarette Smoke Condensate: A Holistic Overview.International journal of molecular sciences · 2023Article
- NS5A domain I antagonises PKR to facilitate the assembly of infectious hepatitis C virus particles.PLoS pathogens · 2023Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interferon (IFN)-induced double-stranded RNA-activated protein kinase PKR mediates inhibition of protein synthesis through phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) and is also involved in the induction of the IFN gene through the activation of the transcription factor NF-kappaB. NF-kappaB is retained in the cytoplasm through binding to its inhibitor IkappaBalpha. The critical step in NF-kappaB activation is the phosphorylation of IkappaBalpha by the IkappaB kinase (IKK) complex. This activity releases NF-kappaB from IkappaBalpha and allows its translocation to the nucleus. Here, we have studied the ability of PKR to activate NF-kappaB in a reporter assay and have shown for the first time that two catalytically inactive PKR mutants, PKR/KR296 and a deletion mutant (PKR/Del42) which lacks the potential eIF2alpha-binding domain, can also activate NF-kappaB. This result indicated that NF-kappaB activation by PKR does not require its kinase activity and that it is independent of the PKR-eIF2alpha relationship. Transfection of either wild-type PKR or catalytically inactive PKR in PKR(0/0) mouse embryo fibroblasts resulted in the activation of the IKK complex. By using a glutathione S-transferase pull-down assay, we showed that PKR interacts with the IKKbeta subunit of the IKK complex. This interaction apparently does not require the integrity of the IKK complex, as it was found to occur with extracts from cells deficient in the NF-kappaB essential modulator, one of the components of the IKK complex. Therefore, our results reveal a novel pathway by which PKR can modulate the NF-kappaB signaling pathway without using its kinase activity.
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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.