PKR signal transduction ; GO:0039585
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PKR SIGNALING OVERVIEW
Protein kinase RNA-activated also known as protein kinase R (PKR)
- PKR can be activated directly by dsRNA or by viral dsRNA replicative intermediates, and indirectly by cytokines or bacterial products such as LPS or lipoprotein.
- Binding to dsRNA is believed to activate PKR by inducing dimerization and subsequent auto-phosphorylation reactions.
- Cytokines and bacterial products activate PKR through upstream activators that could be kinases or other types of protein activators.
- Once active, PKR is able to phosphorylates downstream substrates
- PKR can phosphorylate the eukaryotic translation initiation factor EIF2A to inhibit further translation (and thereby prevent viral protein synthesis)
- PKR can phosphorylate the inhibitory subunit of NFkB (IkB) to mediate the activation of the transcription factor NFkB.
- PKR can feed into JNK/p38 signaling pathways to regulate downstream transcription.
- PKR also mediates apoptosis by regulating FADD, leading to caspase activation.
For image, see: http://viralzone.expasy.org/all_by_protein/554.html Viralzone
GO TERMS
April 2013
[Term] id: GO:0039585 name: PKR signal transduction namespace: biological_process def: "A series of reactions in which a signal is passed on to downstream proteins within the cell via PKR, an intracellular protein kinase that is activated by stress signals or upon binding to double-stranded RNA (dsRNA), followed by autophosphorylation. PKR plays a role in the antiviral response, phosphorylating proteins such as the translation initiation factor eIF2 to inhibit protein synthesis during viral infection. Begins with activation of PKR activity, and ends with regulation of a downstream cellular process, e.g. regulation of transcription or inhibition of translation." [PMID:21204021, PMID:22102852, PMID:9843495, VZ:1576] synonym: "PKR signaling pathway" EXACT [PMID:22102852] synonym: "signaling through PKR" EXACT [GOC:bf] is_a: GO:0035556 ! intracellular signal transduction
QUESTIONS
It's defining signal transduction based on ONE MEDIATOR. So where does PKR signaling begin? The current definition says it begins with activation of PKR, so does this mean that the immediate upstream regulator is a participant in the pathway? Cytokines activate PKR, but quite upstream, so should cytokines be annotate to PKR signaling?
REFERENCES
Signal integration via PKR. PMID 11752661
PKR; a sentinel kinase for cellular stress PMID 10557102