PKR Antibody Phospho (pT446)

Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.

Protein kinase R (PKR) is a serine/threonine kinase that is induced by interferon and activated by double-stranded RNA. Upon activation, PKR is autophosphorylated at multiple sites and phosphorylates the a-subunit of the eukaryotic initiation factor-2 eIF2 (eIF2a), inhibiting protein synthesis (1,2). PKR controls the activation of several transcription factors (1) and mediates the effects of interferon via its capacity to inhibit protein synthesis (2). It has been shown that the autophosphorylation sites Thr-446 and Thr-451 in the activation loop of Human PKR are critical for its kinase activity (3).

A synthetic phospho-peptide corresponding to residues surrounding Thr446 of human PKR (Interferon-inducible RNA-dependent protein kinase) was used as immunogen. The antibody only detects PKR phosphorylated on Threonine 446.

Rabbit

50 mM Tris-Glycine (pH 7.4), 0.15 M NaCl, 40% Glycerol, 0.01% sodium azide and 0.05% BSA.

1. Williams, B.R. PKR; a sentinel kinase for cellular stress. Oncogene 18: 6112<br>2. Cuddihy, A.R., et al. The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro. Oncogene 18:2690-2702 (1999)<br>3. Zhang, F., et al. Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop. J. Biol. Chem. 276:24946-24958 (2001).<br>

Human

Interferon-induced, double-stranded RNA-activated protein kinase, Eukaryotic translation initiation factor 2-alpha kinase 2, eIF-2A protein kinase 2, Interferon-inducible RNA-dependent protein kinase, P1/eIF-2A protein kinase, Protein kinase RNA-activated, PKR, Protein kinase R, Tyrosine-protein kinase EIF2AK2, p68 kinase, EIF2AK2, PKR, PRKR

IHC~~1:50~1:100 WB~~1:1000

Function 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. Cellular_Location Cytoplasm. Nucleus. Cytoplasm, perinuclear region. Note=Nuclear localization is elevated in acute leukemia, myelodysplastic syndrome (MDS), melanoma, breast, colon, prostate and lung cancer patient samples or cell lines as well as neurocytes from advanced Creutzfeldt-Jakob disease patients Tissue_Location Highly expressed in thymus, spleen and bone marrow compared to non-hematopoietic tissues such as small intestine, liver, or kidney tissues. Colocalizes with GSK3B and TAU in the Alzheimer disease (AD) brain. Elevated levels seen in breast and colon carcinomas,and which correlates with tumor progression and invasiveness or risk of progression