title: Phosphorylation of carcinogen metabolizing enzymes: regulation of the phosphorylation status of the major phenobarbital inducible cytochromes P-450 in hepatocytes.
abstract: We present data showing that the major phenobarbital inducible cytochromes P-450 (cytochrome P-450IIB1 and cytochrome P-450IIB2) were phosphorylated in intact hepatocytes. This phosphorylation was greatly increased by the cAMP derivatives N6-dibutyryl-cAMP and 8-thiomethyl-cAMP mediated by a cAMP-dependent protein kinase. Most importantly the phosphorylation status of cytochromes P-450 was shown to change in the hepatocytes after treatment with glucagon, which is known to increase the level of cAMP in hepatocytes. The observed impact of the hormone glucagon on the phosphorylation of distinct cytochrome P-450 forms in intact hepatocytes reveals the possibility that the enzyme activity of cytochromes P-450 could be rapidly and differentially regulated by their phosphorylation and therefore dependent on the hormonal status of the organism.
authors.affiliation: Institute of Toxicology, University of Mainz, FRG.
authors.forename: B
authors.initials: B
authors.lastname: Bartlomowicz
authors.forename: D J
authors.initials: DJ
authors.lastname: Waxman
authors.forename: D
authors.initials: D
authors.lastname: Utesch
authors.forename: F
authors.initials: F
authors.lastname: Oesch
authors.forename: T
authors.initials: T
authors.lastname: Friedberg
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005934:Glucagon / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D013873:Thionucleotides; C011306:8-(methylthio)cyclic 3',5'-adenosine monophosphate; D003994:Bucladesine; D005934:Glucagon; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D006899:Mixed Function Oxygenases; D010634:Phenobarbital