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PKR--a protein kinase regulated by double-stranded RNA
1Department of Cellular and Molecular Sciences, St George's Hospital, Medical School, London, U.K.
Summary
Protein kinase R (PKR) is an interferon-induced enzyme crucial for antiviral defense. It inhibits protein synthesis and regulates cell proliferation, potentially acting as a tumor suppressor.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Protein kinase R (PKR) is an interferon-inducible enzyme found in eukaryotes.
- PKR is activated by double-stranded RNA through autophosphorylation.
- Activated PKR phosphorylates eIF2 alpha, inhibiting protein synthesis.
Purpose of the Study:
- To investigate the biological significance of PKR.
- To explore PKR's role beyond antiviral defense, including cell proliferation and potential tumor suppressor functions.
- To understand PKR's involvement in signal transduction and gene transcription.
Main Methods:
- Utilizing cell lines expressing inactive PKR mutants.
- Employing genetically modified mice with disrupted PKR genes (homozygous disruptions).
Main Results:
- PKR activation inhibits translation by phosphorylating eIF2 alpha.
- Emerging evidence suggests PKR regulates additional substrates.
- PKR influences signal transduction and gene transcription pathways.
Conclusions:
- PKR plays a vital role in the antiviral response mediated by interferons.
- PKR is implicated in regulating cell proliferation in non-infected cells.
- PKR may function as a tumor suppressor under normal physiological conditions.