Phospho-PKR (T258) Polyclonal Antibody, 100µg, (ATB-P0796)

Description

Background:

The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at ‘Tyr-4’ upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at ‘Ser-312’ and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin.

Product datasheet:

Overview
Product Description	Phospho-PKR (T258) Polyclonal Antibody, 100µg, (ATB-P0796)
Image
Species Reactivities	Human
Immunogen	Synthesized peptide derived from human PKR around the phosphorylation site of T258.
Properties
Form	Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide.
Storage Instructions	-20°C/1 year
Clonality	Polyclonal

References:

1. Recombinant modified vaccinia virus Ankara generating excess early double-stranded RNA transiently activates protein kinase R and triggers enhanced innate immune responses. Wolferstätter M, et al. J Virol, 2014 Dec. PMID 25297997
2. Cyclophilin inhibitors reduce phosphorylation of RNA-dependent protein kinase to restore expression of IFN-stimulated genes in HCV-infected cells. Daito T, et al. Gastroenterology, 2014 Aug. PMID 24786893
3. Identification of the PKR nuclear interactome reveals roles in ribosome biogenesis, mRNA processing and cell division. Blalock WL, et al. J Cell Physiol, 2014 Aug. PMID 24347309
4. Inhibition of PKR protects against tunicamycin-induced apoptosis in neuroblastoma cells. Vaughn LS, et al. Gene, 2014 Feb 15. PMID 24334130
5. Protein kinase regulated by dsRNA downregulates the interferon production in dengue virus- and dsRNA-stimulated human lung epithelial cells. Li Y, et al. PLoS One, 2013. PMID 23372823 Free PMC Article
6. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon.
   Meurs E., Chong K., Galabru J., Thomas N.S.B., Kerr I.M., Williams B.R.G., Hovanessian A.G.
   Cell 62:379-390(1990) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 101-118 AND 309-325, INDUCTION.
7. Meurs E.
   Submitted (AUG-1990) to the EMBL/GenBank/DDBJ databasesCited for: SEQUENCE REVISION.
8. Mechanism of interferon action: cDNA structure, expression, and regulation of the interferon-induced, RNA-dependent P1/eIF-2 alpha protein kinase from human cells.
   Thomis D.C., Doohan J.P., Samuel C.E.
   Virology 188:33-46(1992) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
9. Mechanism of interferon action sequence of the human interferon-inducible RNA-dependent protein kinase (PKR) deduced from genomic clones.
   Kuhen K.L., Shen X., Samuel C.E.
   Gene 178:191-193(1996) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
10. Structural organization of the human gene (PKR) encoding an interferon-inducible RNA-dependent protein kinase (PKR) and differences from its mouse homolog.
    Kuhen K.L., Shen X., Carlisle E.R., Richardson A.L., Weier H.-U.G., Tanaka H., Samuel C.E.
    Genomics 36:197-201(1996) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.