ArticleThe Journal of biological chemistry2011
Protein kinase R as mediator of the effects of interferon (IFN) gamma and tumor necrosis factor (TNF) alpha on normal and dysplastic hematopoiesis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Nucleic acid-induced inflammation on hematopoietic stem cells.Experimental hematology · 2024Article
- Interferon-gamma modulates articular chondrocyte and osteoblast metabolism through protein kinase R-independent and dependent mechanisms.Biochemistry and biophysics reports · 2022Article
- Correlation of Body Mass Index and Proinflammatory Cytokine Levels with Hematopoietic Stem Cell Mobilization.Journal of clinical medicine · 2022Article
- PKR kinase directly regulates tau expression and Alzheimer's disease-related tau phosphorylation.Brain pathology (Zurich, Switzerland) · 2021Article
- Role of Extrinsic Apoptotic Signaling Pathway during Definitive Erythropoiesis in Normal Patients and in Patients with β-Thalassemia.International journal of molecular sciences · 2020Review
- The Regulatory Role of IFN-γ on the Proliferation and Differentiation of Hematopoietic Stem and Progenitor Cells.Stem cell reviews and reports · 2017Review
- Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells.Frontiers in oncology · 2017Review
- eIF2α phosphorylation controls thermal nociception.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- IFN-γ-mediated hematopoietic cell destruction in murine models of immune-mediated bone marrow failure.Blood · 2015Article
- Double-stranded RNA-dependent protein kinase deficiency protects the heart from systolic overload-induced congestive heart failure.Circulation · 2014Article
- Programming of fetal insulin resistance in pregnancies with maternal obesity by ER stress and inflammation.BioMed research international · 2014Review
- Signal transduction inhibitors in treatment of myelodysplastic syndromes.Journal of hematology & oncology · 2013Review
- PKR regulates proliferation, differentiation, and survival of murine hematopoietic stem/progenitor cells.Blood · 2013Article
- The protein kinase double-stranded RNA-dependent (PKR) enhances protection against disease cause by a non-viral pathogen.PLoS pathogens · 2013Article
- Regulatory effects of programmed cell death 4 (PDCD4) protein in interferon (IFN)-stimulated gene expression and generation of type I IFN responses.Molecular and cellular biology · 2012Article
- Roles of E4orf6 and VA I RNA in adenovirus-mediated stimulation of human parvovirus B19 DNA replication and structural gene expression.Journal of virology · 2012Article
- Improved control of tuberculosis and activation of macrophages in mice lacking protein kinase R.PloS one · 2012Article
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
Abstract
IFNγ and TNFα are potent inhibitors of hematopoiesis and have been implicated in the pathophysiology of bone marrow failure and myelodysplastic syndromes (MDS). We examined the role of protein kinase R (PKR) in the generation of the inhibitory effects of these myelosuppressive cytokines on hematopoiesis. Our data demonstrate that PKR is rapidly phosphorylated/activated in response to engagement of IFNγ or TNFα receptors in normal human hematopoietic progenitors. Such engagement of PKR is important for the suppressive effects of these cytokines on normal hematopoiesis. Pharmacological targeting of PKR using a specific inhibitor or siRNA-mediated PKR knockdown results in partial reversal of the suppressive effects of IFNγ and TNFα on normal human CD34+-derived myeloid (colony-forming unit-granulocyte-monocytic) and erythroid (burst-forming unit-erythroid) progenitors. Importantly, inhibition of PKR activity or expression increases hematopoietic colony formation from human MDS progenitors, suggesting that drugs that target PKR may provide a novel approach for the treatment of MDS and marrow failure syndromes. Altogether, our data establish that beyond its key role in the induction of IFN-antiviral responses, PKR plays important roles in signaling for IFNγ and other myelosuppressive cytokine receptors as a common mediator of signals for hematopoietic suppression.
Indexed as
Identifiers
What OpenQuestion holds
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.