THE RATPDE3 IVD PHOSPHODIESTERASE GENE CODES FOR MULTIPLE PROTEINS DIFFERENTIALLY ACTIVATED BY CAMP-DEPENDENT PROTEIN-KINASE/

Several mRNAs coding for a cAMP-specific phosphodiesterase (ratPDE3/IV d) with divergent 5' regions have been detected in mammalian cells. To determine the physiological significance of these differences, the ex pression of these mRNAs and the properties of the corresponding protei ns were investigated. At least three mRNA species derived from the rat PDE3/IVd gene (ratPDE3.1, ratPDE3.2, and ratPDE3.3 mRNAs) are present in Sertoli and thyroid cells and in brain. Expression of ratPDE3.1 and ratPDE3.2 but not ratPDE3.3 mRNAs was dependent on hormone stimulatio n. The ratPDE3.2 and ratPDE3.3 mRNA variants were translated into poly peptides with immunochemical and biochemical properties identical to t he native cAMP phosphodiesterases (PDEs) found in the Sertoli cell and thyroid FRTL-5 cells. Incubation of the recombinant PDEs with the cat alytic subunit of the cAMP-dependent protein kinase in a cell-free sys tem caused the phosphorylation and activation of the ratPDE3.3 protein variant. Under the same experimental conditions, ratPDE3.1 and ratPDE 3.2 protein variants were neither phosphorylated nor activated by the cAMP-dependent protein kinase. Similar results were obtained by stimul ating cells expressing the three recombinant PDE variants with dibutyr yl cAMP. These findings demonstrate that the ratPDE3/IVd gene codes fo r PDE forms subject to different regulations.