scholarly journals Role of Double-Stranded RNA-Activated Protein Kinase R (PKR) in Deoxynivalenol-Induced Ribotoxic Stress Response

2003 ◽  
Vol 74 (2) ◽  
pp. 335-344 ◽  
Author(s):  
H.-R. Zhou ◽  
A. S. Lau ◽  
J. J. Pestka
Keyword(s):  
Stress Response ◽  
Protein Kinase ◽  
Protein Kinase R ◽  
Double Stranded Rna ◽  
Ribotoxic Stress Response

scholarly journals Role of protein kinase R in double-stranded RNA-induced expression of nitric oxide synthase in human astroglia

FEBS Letters ◽  
2004 ◽  
Vol 563 (1-3) ◽  
pp. 223-228 ◽  
Author(s):  
Corey J Auch ◽  
Ramendra N Saha ◽  
Faruk G Sheikh ◽  
Xiaojuan Liu ◽  
Bertram L Jacobs ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Nitric Oxide Synthase ◽  
Protein Kinase R ◽  
Induced Expression ◽  
Double Stranded Rna ◽  
Oxide Synthase

scholarly journals Hepatic stellate cell proliferation: A potential role of protein kinase R

Hepatology ◽  
2011 ◽  
Vol 54 (4) ◽  
pp. 1484-1485 ◽  
Author(s):  
Sara Ceccarelli ◽  
Nadia Panera ◽  
Anna Alisi ◽  
Valerio Nobili
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Hepatic Stellate Cell ◽  
Potential Role ◽  
Stellate Cell ◽  
Protein Kinase R

scholarly journals The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration

2021 ◽  
Vol 13 ◽  
Author(s):  
Nicolás W. Martinez ◽  
Felipe E. Gómez ◽  
Soledad Matus
Keyword(s):  
Protein Kinase ◽  
Pathological Process ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Protein Kinase R ◽  
Eukaryotic Translation ◽  
Neurodegenerative Process ◽  
Age Related ◽  
Initiation Factor 2

There is a growing evidence describing a decline in adaptive homeostasis in aging-related diseases affecting the central nervous system (CNS), many of which are characterized by the appearance of non-native protein aggregates. One signaling pathway that allows cell adaptation is the integrated stress response (ISR), which senses stress stimuli through four kinases. ISR activation promotes translational arrest through the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α) and the induction of a gene expression program to restore cellular homeostasis. However, depending on the stimulus, ISR can also induce cell death. One of the ISR sensors is the double-stranded RNA-dependent protein kinase [protein kinase R (PKR)], initially described as a viral infection sensor, and now a growing evidence supports a role for PKR on CNS physiology. PKR has been largely involved in the Alzheimer’s disease (AD) pathological process. Here, we reviewed the antecedents supporting the role of PKR on the efficiency of synaptic transmission and cognition. Then, we review PKR’s contribution to AD and discuss the possible participation of PKR as a player in the neurodegenerative process involved in aging-related pathologies affecting the CNS.

The Role of Protein Kinase R in the Interferon Response

2011 ◽  
Vol 31 (1) ◽  
pp. 59-70 ◽  
Author(s):  
Agnieszka Pindel ◽  
Anthony Sadler
Keyword(s):  
Protein Kinase ◽  
Interferon Response ◽  
Protein Kinase R

Role of the AMP-activated protein kinase in the cellular stress response

1994 ◽  
Vol 4 (4) ◽  
pp. 315-324 ◽  
Author(s):  
Julia M. Corton ◽  
John G. Gillespie ◽  
D.Grahame Hardie
Keyword(s):  
Stress Response ◽  
Protein Kinase ◽  
Cellular Stress ◽  
Cellular Stress Response ◽  
Amp Activated Protein Kinase

scholarly journals Analysis of High-Affinity Binding of Protein Kinase R to Double-Stranded RNA

Biochemistry ◽  
2012 ◽  
Vol 51 (44) ◽  
pp. 8764-8770 ◽  
Author(s):  
Bushra Husain ◽  
Ishita Mukerji ◽  
James L. Cole
Keyword(s):  
Protein Kinase ◽  
Affinity Binding ◽  
Protein Kinase R ◽  
High Affinity Binding ◽  
Double Stranded Rna ◽  
High Affinity

scholarly journals Protein Kinase R Mediates Intestinal Epithelial Gene Remodeling in Response to Double-Stranded RNA and Live Rotavirus

2005 ◽  
Vol 174 (10) ◽  
pp. 6322-6331 ◽  
Author(s):  
Matam Vijay-Kumar ◽  
Jon R. Gentsch ◽  
William J. Kaiser ◽  
Niels Borregaard ◽  
Margaret K. Offermann ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Intestinal Epithelial ◽  
Protein Kinase R ◽  
Double Stranded Rna

scholarly journals Binding and Nuclear Relocalization of Protein Kinase R by Human Cytomegalovirus TRS1

2006 ◽  
Vol 80 (23) ◽  
pp. 11817-11826 ◽  
Author(s):  
Morgan Hakki ◽  
Emily E. Marshall ◽  
Katherine L. De Niro ◽  
Adam P. Geballe
Keyword(s):  
Protein Kinase ◽  
Human Cytomegalovirus ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Underlying Mechanism ◽  
Cellular Protein ◽  
Initiation Factor ◽  
Protein Kinase R ◽  
Double Stranded Rna

ABSTRACT The human cytomegalovirus (HCMV) TRS1 and IRS1 genes block the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2α) and the consequent shutoff of cellular protein synthesis that occur during infection with vaccinia virus (VV) deleted of the double-stranded RNA binding protein gene E3L (VVΔE3L). To further define the underlying mechanism, we first evaluated the effect of pTRS1 on protein kinase R (PKR), the double-stranded RNA (dsRNA)-dependent eIF2α kinase. Immunoblot analyses revealed that pTRS1 expression in the context of a VVΔE3L recombinant decreased levels of PKR in the cytoplasm and increased its levels in the nucleus of infected cells, an effect not seen with wild-type VV or a VVΔE3L recombinant virus expressing E3L. This effect of pTRS1 was confirmed by visualizing the nuclear relocalization of PKR-EGFP expressed by transient transfection. PKR present in both the nuclear and cytoplasmic fractions was nonphosphorylated, indicating that it was unactivated when TRS1 was present. PKR also accumulated in the nucleus during HCMV infection as determined by indirect immunofluorescence and immunoblot analysis. Binding assays revealed that pTRS1 interacted with PKR in mammalian cells and in vitro. This interaction required the same carboxy-terminal region of pTRS1 that is necessary to rescue VVΔE3L replication in HeLa cells. The carboxy terminus of pIRS1 was also required for rescue of VVΔE3L and for mediating an interaction of pIRS1 with PKR. These results suggest that these HCMV genes directly interact with PKR and inhibit its activation by sequestering it in the nucleus, away from both its activator, cytoplasmic dsRNA, and its substrate, eIF2α.

Tumour necrosis factor α up-regulates protein kinase R (PKR)-activating protein (PACT) and increases phosphorylation of PKR and eukaryotic initiation factor 2-α in articular chondrocytes

2002 ◽  
Vol 30 (6) ◽  
pp. 886-889 ◽  
Author(s):  
S. J. Gilbert ◽  
V. C. Duance ◽  
D. J. Mason
Keyword(s):  
Protein Kinase ◽  
Tumour Necrosis ◽  
Cartilage Degradation ◽  
Initiation Factor ◽  
Tumour Necrosis Factor Α ◽  
Protein Kinase R ◽  
Initiation Factor 2 ◽  
Factor Α ◽  
Necrosis Factor

Our previous analysis of the genes regulated in cartilage at the onset of spontaneous osteoarthritis in the guinea pig knee revealed up-regulation of the gene for protein kinase R (PKR)-activating protein (PACT), which encodes the cellular activator of the protein kinase, PKR. PACT and PKR are upstream components of a number of signal transduction and gene transcription pathways used by pro-inflammatory cytokines. We have investigated the role of PACT and PKR in articular cartilage degradation using cytokine treatment of bovine primary chondrocytes and cartilage explants. Tumour necrosis factor α increased expression of PACT protein after 3 h of treatment. Furthermore, increased phosphorylation of PKR and eukaryotic initiation factor 2-α was observed. The known role of PKR in cytokine-induced signalling pathways, together with our data showing cytokine regulation of PACT and PKR in chondrocytes, reveals a novel mechanism of cartilage degradation that may be important in the pathogenesis of arthritic diseases.

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