Catalytic subunit of cAMP‐dependent protein kinase is essential for cAMP‐mediated mammalian gene expression

Abstract

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.