Abstract
The protein kinase R (PKR) is an intracellular sensor of stress, exemplified by viral infection. Double-stranded (ds) RNA produced during viral replication activates PKR, which in turn arrests protein synthesis by phosphorylating the α subunit of the translation initiation factor eIF2. As well as dsRNA, two additional ligands, PACT and heparin, directly activate the kinase. These mediate the response of PKR to additional indirect stimuli, including bacterial lipopolysaccharides, ceramide and polyanionic molecules. This responsiveness to multiple stimuli advocates a broader role for PKR as a signalling molecule for diverse physiological stresses. Appropriately, a number of other protein substrates have been reported for PKR. These substrates support additional roles for PKR in the regulation of transcription and signal transduction in infected cells, as well as uninfected but diseased tissues, such as in tumorigenesis and neurodegenerative diseases. Finally, PKR plays a role in normal cell differentiation in platelet-derived growth factor signalling and in osteoblast-mediated calcification.
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Abbreviations
- AT:
-
Amino-terminal heparin-binding domain
- CTD:
-
Carboxy-terminal heparin-binding domain
- dsRNA:
-
Double-stranded RNA
- FA:
-
Fanconi anaemia
- FADD:
-
Fas-associated death domain
- GCN2:
-
General control non-de-repressible 2
- HCV:
-
Hepatitis C virus
- HDV:
-
Hepatitis D virus
- HIV:
-
Human immunodeficiency virus
- HRI:
-
Heme-regulated inhibitor
- IFN:
-
Interferon
- IRF:
-
IFN regulatory factor
- ISRE:
-
Interferon stimulatory response element
- KCS:
-
Kinase conserved sequence element
- LTR:
-
Long terminal repeat
- MEF:
-
Mouse embryonic fibroblasts
- NF-κB:
-
Nuclear factor κ B
- NF90:
-
Nuclear factor 90
- PDGF:
-
Platelet-derived growth factor
- PERK:
-
PKR-like endoplasmic reticulum kinase
- PKR:
-
Protein kinase R
- RBD:
-
dsRNA-binding domain
- RBMs:
-
dsRNA-binding motifs
- S-HDAg:
-
Hepatitis D virus small delta antigen
- siRNA:
-
Small interfering RNA
- SPNR:
-
Spermatid perinuclear RNA-binding protein
- TNFα:
-
Tumour necrosis factor α
- TRAF:
-
TNF receptor-associated factor
- TRBP:
-
TAR RNA-binding protein
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© 2007 Springer-Verlag Berlin Heidelberg
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Sadler, A.J., Williams, B. (2007). Structure and Function of the Protein Kinase R. In: Pitha, P.M. (eds) Interferon: The 50th Anniversary. Current Topics in Microbiology and Immunology, vol 316. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71329-6_13
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DOI: https://doi.org/10.1007/978-3-540-71329-6_13
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-71328-9
Online ISBN: 978-3-540-71329-6
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