Structure and Function of the Protein Kinase R

  • A. J. Sadler
  • B. R. G. Williams
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 316)

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.

Keywords

Fatigue Tyrosine Adduct Serine Oncol 

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • A. J. Sadler
    • 1
  • B. R. G. Williams
    • 1
  1. 1.Monash Institute of Medical ResearchMonash UniversityMelbourneAustralia

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