| Description |
FN-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 (PMID:18835251, PMID:19507191, PMID:19189853, PMID:21123651, PMID:21072047, PMID:22948139, PMID:23229543, PMID: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 (PMID:19189853, PMID:21123651, PMID:22948139, PMID: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) (PMID:11836380, PMID:19189853, PMID:20171114, PMID:19840259, PMID:21710204, PMID:23115276, PMID: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 (PMID:11836380, PMID:22214662, PMID: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 (PMID: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 (PMID:22948139, PMID:23084476, PMID: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 (PMID:10848580, PMID:15121867, PMID:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PMID: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) (PMID:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PMID: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. |
| Other names |
EIF2AK2, 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, EIF2AK2, PKR, PRKR |
