title: The protein kinase C inhibitors Ro 318220 and GF 109203X are equally potent inhibitors of MAPKAP kinase-1beta (Rsk-2) and p70 S6 kinase.
abstract: The protein kinase C (PKC) inhibitors Ro 318220 and GF 109203X have been used in over 350 published studies to investigate the physiological roles of PKC. Here we demonstrate that these inhibitors are not selective for PKC isoforms as was previously assumed. Ro 318220 inhibited MAPKAP kinase-1beta (also known as Rsk-2) in vitro (IC50 3nM) more potently than it inhibited mixed PKC isoforms (IC50 5 nM), and it also inhibited p70 S6 kinase (IC50 15 nM). GF 109203X also potently inhibited MAPKAP kinase-1beta (IC50 50 nM) and p70 S6 kinase (IC50 100 nM) with similar potency to PKC isoforms (IC50 30 nM). The inhibition of MAPKAP kinase-1beta, p70 S6 kinase, and probably other protein kinases, may explain many of the effects previously attributed to PKC.
authors.affiliation: Department of Biochemistry, University of Dundee, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Alessi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008301:Maleimides / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D019893:Ribosomal Protein S6 Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D018411:Spodoptera; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D010455:Peptides; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; C064758:Ro 31-8220