title: Nitric oxide: a regulator of eukaryotic initiation factor 2 kinases.
abstract: Generation of nitric oxide (NO(•)) can upstream induce and downstream mediate the kinases that phosphorylate the α subunit of eukaryotic initiation factor 2 (eIF2α), which plays a critical role in regulating gene expression. There are four known eIF2α kinases (EIF2AKs), and NO(•) affects each one uniquely. Whereas NO(•) directly activates EIF2AK1 (HRI), it indirectly activates EIF2AK3 (PERK). EIF2AK4 (GCN2) is activated by depletion of l-arginine, which is used by nitric oxide synthase (NOS) during the production of NO(•). Finally EIF2AK2 (PKR), which can mediate inducible NOS expression and therefore NO(•) production, can also be activated by NO(•). The production of NO(•) and activation of EIF2AKs coordinately regulate physiological and pathological events such as innate immune response and cell apoptosis.
authors.affiliation: Edison Biotechnology Institute and Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA.
authors.forename: Lingying
authors.initials: L
authors.lastname: Tong
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Heim
authors.forename: Shiyong
authors.initials: S
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D001120:Arginine / Q000378:metabolism; D002453:Cell Cycle; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D005609:Free Radicals; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D001120:Arginine; D015852:Eukaryotic Initiation Factor-2; D005609:Free Radicals; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; C529271:EIF2AK4 protein, human