Isoform specificity of activators and inhibitors of protein kinase C gamma and delta.
Expression of certain mammalian protein kinase C (PKC) isoforms inhibits the proliferation of Schizosaccharomyces pombe (Goode et al., Mol. Biol. Cell 5 (1994) 907-920). We have taken advantage of this fact to determine the in vivo isoform preference of a number of PKC inhibitors, using a microtitre plate assay which allows rapid screening. This in vivo model has revealed previously unreported preferences; calphostin C is a more efficient inhibitor of the novel PKCS than chelerythrine chloride whereas the efficiencies are reversed for inhibition of the classical PKCgamma. We have also shown that the anti-leukaemic agent bryostatin 1 inhibits or activates in vivo in an isoform-specific manner.
Keenan
C
C
Biochemistry Department, Oxford University, UK.
Goode
N
N
Pears
C
C
D000098:Acetophenones / Q000494:pharmacology; D000470:Alkaloids; D053119:Benzophenanthridines; D001578:Benzopyrans / Q000494:pharmacology; D054713:Bryostatins; D002227:Carbazoles / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D008301:Maleimides / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051745:Protein Kinase C-delta; D011994:Recombinant Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000254:growth & development; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014170:Transformation, Genetic
D000098:Acetophenones; D000470:Alkaloids; D053119:Benzophenanthridines; D001578:Benzopyrans; D054713:Bryostatins; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D007783:Lactones; D018942:Macrolides; D008301:Maleimides; D009281:Naphthalenes; D010617:Phenanthridines; D011994:Recombinant Proteins; C081021:Go 6976; C046785:bryostatin 1; C085746:rottlerin; C016299:chelerythrine; C087857:protein kinase C gamma; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C058819:calphostin C; C088060:bisindolylmaleimide; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate