title: Halogenated benzimidazole inhibitors of phosphorylation, in vitro and in vivo, of the surface acidic proteins of the yeast ribosomal 60S subunit by endogenous protein kinases CK-II and PK60S.
abstract: Several halogeno benzimidazoles and 2-azabenzimidazoles, previously shown to be relatively selective inhibitors of protein kinases CK-I and/or CK-II from various sources, including CK-II from yeast [Szyszka et al. (1995) Biochem. Biophys. Res. Commun. 208, 418-424] inhibit also the yeast ribosomal protein kinase PK60S. The most effective inhibitor of CK-II and PK60S was tetrabromo-2-azabenzimidazole ](TetraBr-2-azaBz), which was competitive with respect to ATP (and GTP in the case of CK-II) with Ki values of 0.7 microM for CK-II, and 0.1 microM for PK60S PK60S phosphorylates only three (YP1 beta', YP2 alpha) out of five polypeptides of pp13 kDa acidic proteins of 60S subunit phosphorylated by CK-II [Szyszka et al. (1995) Acta Biochim. Polon. 42, 357-362]. Accordingly, TetraBr-2-azaBz inhibits phosphorylation only of these polypeptides, catalysed by PK60S . Addition of TetraBr-2-azaBz to cultures of yeast cells, at concentrations which were without effect on cell growth, led to inhibition of intracellular phosphorylation of ribosomal acidic proteins, paralleling that observed in vitro. TetraBr-2-azaBz is shown to be a useful tool for studies on the intracellular regulation of phosphorylation of the ribosomal 60S acidic proteins, which are involved in formation of active ribosomes.
authors.affiliation: Department of Molecular Biology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Szyszka
authors.forename: A
authors.initials: A
authors.lastname: Boguszewska
authors.forename: D
authors.initials: D
authors.lastname: Shugar
authors.forename: N
authors.initials: N
authors.lastname: Grankowski
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006219:Halogens / Q000737:chemistry* / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D014230:Triazoles / Q000494:pharmacology
chemical_list: C103118:4,5,6,7-tetrabromo-2-azabenzimidazole; D001562:Benzimidazoles; D005656:Fungal Proteins; D006219:Halogens; D010446:Peptide Fragments; D012269:Ribosomal Proteins; D014230:Triazoles; C083550:60S ribosomal protein kinase; D017346:Protein Serine-Threonine Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases