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Interaction Network for EIF2AK2

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Role of PKR in Interferon Induction and Antiviral Response
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PKR Pathway

Synonyms: 2310047A08Rik, 4732414G15Rik, AI467567, AI747578, DAI, DOUBLE STRANDED RNA DEPENDENT PROTEIN KINASE, EIF2AK1, EIF2AK2, GCN4, IFNPKR, MGC126524, p68 kinase, PKR, PRKR, Tik

PKR Pathway

PKR, dsRNA-dependent serine/threonine protein kinase R, (P1 Kinase; P1/eIF-2alpha kinase; p68; p67; DAI, ds1, or TIK) responds to stress signals by modulating protein synthesis, cell survival status and gene expression. PKR is a central mediator of cellular responses to viral infection and/or environmental stress. Viral infections induce expression and secretion of interferon gamma (IFN-gamma) from host cells. IFNγ induces PKR. PKR is activated by double-stranded RNA (dsRNA) and/or protein kinase, interferon-inducible double stranded RNA dependent activator, PACT (RAX), which signal viral infection or cell stress, respectively. Brief PKR activation is anti-apoptotic. Prolonged PKR activation is pro-apoptotic.

Early stimulation of PKR inhibits apoptosis by inducing the release of NFkappaB (p50/p65) heterodimer from IkappaB. Prolonged stimulation of PKR inhibits the initiation of RNA translation by phosphorylating eIF2alpha (eIF2α component of the eIF2 initiation complex. Inhibition of protein translation and prolonged PKR activation induce apoptosis through a series of down-stream pathways: the release of NFkappaB (p50/cRel), a pro-apoptotic heterodimer; activation of protein phosphatase 2A (PP2A), activation of MAPK pathways, JNK and p38; down-regulation of p53, and inhibition of signal transducer and activator of transcription-1 and -3 (STAT1 and STAT3).


References:

  1. Bennett, R. L. et. al. (2006) RAX, the PKR activator, sensitizes cells to inflammatory cytokines, serum withdrawal, chemotherapy, and viral infection. Blood. 108, 821-829.   

  2. Donze, O. et. al. (2004) The protein kinase PKR: a molecular clock that sequentially activates survival and death programs. EMBO J. 23, 564-571.  

  3. Guerra, S. et. al. (2006) Human gene profiling in response to the active protein kinase, interferon-induced serine/threonine protein kinase (PKR), in infected cells. Involvement of the transcription factor ATF-3 IN PKR-induced apoptosis. J. Biol. Chem. 281, 18734-18745.

  4. Li, S. et. al. (2006) Molecular basis for PKR activation by PACT or dsRNA. Proc. Natl. Acad. Sci. U S A. 103, 10005-10010.
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Content for this page is provided by Dennis R. Conrad, Ph.D., a Life Science industry consultant with over 25 years of experience in the formulation and optimization of cell culture media. Dr. Conrad's email address is biomediaexpert@earthlink.net