Molecular interaction between cAMP and calcium in calmodulin-dependent cyclic nucleotide phosphodiesterase system.

The second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. cAMP acts on protein kinases, and Ca2+ works through a ubiquitous calcium-binding protein, calmodulin. The 2 systems are not independent, however, but interact in several important fashions. These interactions can be demonstrated by calmodulin-dependent phosphodiesterase. The bovine heart calmodulin-dependent phosphodiesterase can be phosphorylated by cAMP-dependent protein kinase, resulting in a decrease in the enzyme's affinity for calmodulin. The phosphorylation of calmodulin-dependent phosphodiesterase is blocked by Ca2+ and calmodulin, and reversed by the calmodulin-dependent phosphatase (calcineurin). The dephosphorylation is accompanied by an increase in the affinity of the phosphodiesterase for calmodulin. Results from this study suggest that the activity of this phosphodiesterase is precisely regulated by cross-talk between Ca2+ and cAMP signalling pathways.