Activities of cAMP-dependent protein kinase and enzymes of 2',5'-oligoadenylate metabolism in NIH 3T3 cells deepening into the resting state.

The activity of cAMP-dependent protein kinase was found to increase continuously in the NIH 3T3 cells, deepening into the resting state. The increase correlated with intracellular level of heat-stable protein inhibitor of the protein kinase rather than with the cAMP content. The elevation of 2',5'-oligo(A) synthetase activity and the decrease in 2'-phosphodiesterase activity were also observed in the cells sinking into the resting state.

Regulation of 2-5 A phosphodiesterase activity by cAMP-dependent phosphorylation: mechanism and biological role.

The results of the present study permit the explanation of one of the mechanisms of the interconnection between the regulatory systems of cAMP and 2-5A. cAMP-dependent regulation of 2'-PDE was found to involve phosphorylation of the specific protein inhibitor. Originally, a similar way of regulation of the enzyme activity was discovered for protein phosphatase I.

Inhibition of 2'-phosphodiesterase by cAMP-dependent protein kinase. Involvement of phosphorylation of protein inhibitor.

2'-Phosphodiesterase from NIH 3T3 cells was purified about 530-fold. Treatment of the cell lysate with the cAMP-dependent protein kinase causing the 2'-phosphodiesterase inhibition did not result in phosphorylation of the enzyme itself. The kinase was found to phosphorylate a specific 18-kDa protein, the phosphorylated form of this protein being the inhibitor of 2'-phosphodiesterase.

The mechanisms of the cyclic AMP-dependent regulation of the enzymes of the 2',5'-oligoadenylate system.

The cAMP-dependent induction of 2,5-oligoadenylate (2-5A) synthetase and cAMP-dependent inhibition of 2-5A phosphodiesterase are shown. Variations in activities of cAMP-dependent protein kinase and the enzymes of 2-5A metabolism in the cells deepening into the resting state were found to be compatible with the above finding. A scheme of coordinated action of cAMP and 2-5A is proposed.