Differential response of type I and type II cyclic AMP-dependent protein kinases in submandibular gland of isoproterenol-treated rats.

The cytosolic protein kinase isozymes were studied in relation to the secretion of saliva and the proliferative process induced by isoproterenol. At the same time as salivary secretion began, cytosolic protein kinase was activated and, in the absence of cyclic AMP, increased to a maximum level at 10 min after administration of the drug. The active state of the enzyme was maintained for 1-2 h. Chromatographic analysis of the cytosol enzyme revealed that in an activated state type II kinase easily dissociates into the catalytic and regulatory subunits while type I kinase hardly dissociates. Thus we conclude that type I kinase, at least in submandibular gland, is less dissociable in the presence of cyclic AMP than type II kinase but highly active in a ternary complex (R2-4 cAMP-C2). The presence of cyclic AMP-independent protein kinase, which co-chromatographed with protein kinase II, was demonstrated by use of a heat-stable inhibitor from bovine muscle, which totally inhibited the cyclic AMP-dependent enzymes, but stimulated the cyclic AMP-independent protein kinase. The level of protein kinase I decreased to its lowest value, about half that of the control value, at 10 h after isoproterenol injection and then increased slightly at 15 h, whereas type II kinase remained virtually unchanged, suggesting that the two protein kinase isozymes are independently regulated in the proliferating cells.