title: A type 1 phosphoprotein phosphatase active with phosphorylated Mr = 68,000 initiation factor 2 kinase.
abstract: A type 1 protein phosphatase from reticulocytes is shown to efficiently dephosphorylate the Mr = 68,000 phosphopeptide of the double-stranded RNA-dependent kinase that phosphorylates the alpha subunit of eukaryotic peptide initiation factor 2, eIF-2. The kinase, activated in the presence of double-stranded RNA with concomitant phosphorylation of the Mr = 68,000 peptide, causes inhibition of peptide initiation and thereby effects translational control of protein synthesis. The Mn2+-dependent phosphatase is classified as a type 1 enzyme in that it is inhibited by inhibitor 2 in nanomolar concentrations and appears to have a Mr = 35,000 catalytic subunit. Dephosphorylation of the Mr = 68,000 peptide by the phosphatase is directly associated with a loss in kinase activity which can be restored by incubation with double-stranded RNA in the presence of ATP. The results demonstrate that the eIF-2 alpha kinase can undergo cyclic activation-inactivation that appears to be directly related to the phosphorylation state of the Mr = 68,000 peptide. They strongly support the previous conclusion that double-stranded RNA is required only for activation of the kinase and phosphorylation of the Mr = 68,000 peptide.
authors.affiliation: Clayton Foundation Biochemical Institute, Chemistry Department, University of Texas, Austin 78712.
authors.forename: R
authors.initials: R
authors.lastname: Szyszka
authors.forename: W
authors.initials: W
authors.lastname: Kudlicki
authors.forename: G
authors.initials: G
authors.lastname: Kramer
authors.forename: B
authors.initials: B
authors.lastname: Hardesty
authors.forename: J
authors.initials: J
authors.lastname: Galabru
authors.forename: A
authors.initials: A
authors.lastname: Hovanessian
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008345:Manganese / Q000494:pharmacology; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000201:enzymology; D013379:Substrate Specificity; D019892:eIF-2 Kinase
chemical_list: D008345:Manganese; D011494:Protein Kinases; D019892:eIF-2 Kinase; D010749:Phosphoprotein Phosphatases