EIF2AK2, EnkiLife, AMRe05976

PKR a protein kinase of the PEK family. Upon binding double-stranded RNA, it becomes autophosphorylated and activated. Phosphorylates and inhibits the alpha subunit of eIF2 alpha, which leads to an inhibition of the initiation of protein synthesis. IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed: 18835251, PubMed: 19507191, PubMed: 19189853, PubMed: 21123651, PubMed: 21072047, PubMed: 22948139, PubMed: 23229543, PubMed: 22381929). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2- alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed: 19189853, PubMed: 21123651, PubMed: 22948139, PubMed: 23229543). 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) (PubMed: 11836380, PubMed: 19189853, PubMed: 20171114, PubMed: 19840259, PubMed: 21710204, PubMed: 23115276, PubMed: 23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed: 11836380, PubMed: 22214662, PubMed: 19229320). 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 (PubMed: 20395957). 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 (PubMed: 22948139, PubMed: 23084476, PubMed: 23372823). 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 (PubMed: 10848580, PubMed: 15121867, PubMed: 15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed: 20685959). 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) (PubMed: 20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed: 22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity).