[22] Substrate-Directed Regulation of cAMP-Dependent Phosphorylation

This chapter explains the substrate-directed regulation of cAMP-dependent phosphorylation. Although there are only a limited number of reports on effector-directed modulation of cAMP-dependent phosphorylation, a number of general observations can be made. Many proteins, which are subject to protein kinase-catalyzed phosphorylation exhibit allosteric properties—that is, they interact with low-molecular-weight ligands and undergo conformational changes resulting in transitions between active and inactive forms. When studying substrate-directed phosphorylation, it is important to remove all endogenous phosphate from the enzyme preparation. In addition, the concentrations of the effectors tested should be within the known physiological range. Whether effector-modulated phosphorylation of enzymes is important in the physiological modulation of enzyme activity is uncertain, but such modulation has been shown to occur in intact cells. Examination of additional proteins reveals that substrate-directed regulation of phosphorylation is widespread and is important in the in vivo regulation of enzyme activity.