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Phosphorylable tyrosine residue 162 in the double-stranded RNA-dependent kinase PKR modulates its interaction with SUMO
- Source :
- Scientific Reports, Scientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Activated dsRNA-dependent serine/threonine kinase PKR phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2α), resulting in a shut-off of general translation, induction of apoptosis, and inhibition of virus replication. PKR can be activated by binding to dsRNA or cellular proteins such as PACT/RAX, or by its conjugation to ISG15 or SUMO. Here, we demonstrate that PKR also interacts with SUMO in a non-covalent manner. We identify the phosphorylable tyrosine residue 162 in PKR (Y162) as a modulator of the PKR-SUMO non-covalent interaction as well as of the PKR SUMOylation. Finally, we show that the efficient SUMO-mediated eIF2α phosphorylation and inhibition of protein synthesis induced by PKR in response to dsRNA depend on this residue. In summary, our data identify a new mechanism of regulation of PKR activity and reinforce the relevance of both, tyrosine phosphorylation and SUMO interaction in controlling the activity of PKR.
- Subjects :
- 0301 basic medicine
viruses
SUMO-1 Protein
SUMO protein
lcsh:Medicine
Apoptosis
environment and public health
Article
Mice
eIF-2 Kinase
03 medical and health sciences
chemistry.chemical_compound
Animals
Humans
Phosphorylation
Tyrosine
lcsh:Science
RNA, Double-Stranded
G alpha subunit
Mice, Knockout
Multidisciplinary
030102 biochemistry & molecular biology
Chemistry
Kinase
lcsh:R
Sumoylation
virus diseases
Translation (biology)
Tyrosine phosphorylation
biochemical phenomena, metabolism, and nutrition
Protein kinase R
Cell biology
Enzyme Activation
enzymes and coenzymes (carbohydrates)
HEK293 Cells
030104 developmental biology
lcsh:Q
Protein Binding
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....eeb280d6b5e31ff646387536e0a61a66