Catalytic subunit of cAMP-dependent protein kinase is essential for cAMP-mediated mammalian gene expression.
Cyclic AMP-stimulated mRNA levels in cultured rat hepatocytes were inhibited by three different inhibitors of cAMP-dependent protein kinase activity: (i) Rp-cAMPS, a cAMP analog with a sulfur substitution at the equatorial oxygen of the cyclic monophosphate; (ii) H8, an isoquinoline sulfonamide derivative; and (iii) PKI, a 20-amino acid synthetic peptide of the Walsh protein kinase inhibitor. These inhibitors specifically blocked the cAMP-stimulated increase in mRNA for tyrosine aminotransferase and phosphoenolpyruvate carboxykinase; they had no effect on the level of albumin mRNA which is not cAMP regulated. These results provide functional evidence that kinase activity involving protein phosphorylation is required in cAMP-mediated gene expression in mammalian cells.
Büchler
W
W
Labor für Klinische Biochemie, Medizinische Universitätsklinik, Würzburg, FRG.
Walter
U
U
Jastorff
B
B
Lohmann
S M
SM
D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic
D012333:RNA, Messenger; D000242:Cyclic AMP; D011494:Protein Kinases