Cyclic AMP-dependent protein kinase does not regulate CTP:phosphocholine cytidylyltransferase activity in maturing type II cells.

CTP:phosphocholine cytidylyltransferase catalyses a rate regulatory step in the de novo synthesis of surfactant phosphatidylcholine in alveolar type II cells. To investigate if cytidylyltransferase can be regulated by cAMP-dependent protein kinase, we first studied the ontogeny of cAMP-dependent protein kinase activity in type II cells of fetal rat lung. Total cAMP-dependent protein kinase activity, measured in the presence of 10 microM cAMP, as well as endogenous activity, measured without cAMP, increased with advancing gestation. Phosphocholine cytidylyltransferase activity showed a similar developmental profile. This temporal relationship between cAMP-dependent protein kinase and cytidylyltransferase supports a potential role for cAMP-dependent protein kinase in regulating cytidylyltransferase phosphorylation. Cytidylyltransferase purified from adult rat lung was, indeed, phosphorylated in vitro by cAMP-dependent protein kinase. Despite the phosphorylation, however, no change in cytidylyltransferase activity was noted. Pre-incubation of fetal type II cell cytosol with ATP and Mg2+ did not affect cytidylyltransferase activity. Addition of either cAMP, dibutyryl-cAMP or the catalytic subunit of cAMP-dependent protein kinase to the pre-incubation medium did also not alter cytidylyltransferase activity. Furthermore, neither cAMP-dependent protein kinase inhibitor peptide, nor H8, a cyclic nucleo-dependent protein kinase inhibitor, affected cytidylyltransferase activity in fetal type II cell cytosol. Treatment of intact fetal type II cells with either cAMP, dibutyryl-cAMP or 8-[4-chlorophenylthio]cAMP activated cAMP-dependent protein kinase activity but did not alter cytidylyltransferase activity. We conclude that the increase in cytidylyltransferase activity in fetal type II cells at late gestation is not regulated by the developmental activation of cAMP-dependent protein kinase.