The role of protein phosphorylation in the regulation of cyclic nucleotide phosphodiesterases.
The cyclic nucleotide phosphodiesterases constitute a complex superfamily of enzymes responsible for catalyzing the hydrolysis of cyclic nucleotides. Regulation of cyclic nucleotide phosphodiesterases is one of the two major mechanisms by which intracellular cyclic nucleotide levels are controlled. In many cases the fluctuations in cyclic nucleotide levels in response to hormones is due to the hormone responsiveness of the phosphodiesterase. Isozymes of the cGMP-inhibited, cAMP-specific, calmodulin-stimulated and cGMP-binding phosphodiesterases have been demonstrated to be substrates for protein kinases. Here we review the evidence that hormonally responsive phosphorylation acts to regulate cyclic nucleotide phosphodiesterases. In particular, the cGMP-inhibited phosphodiesterases, which can be phosphorylated by at least two different protein kinases, are activated as a result of phosphorylation. In contrast, phosphorylation of the calmodulin-stimulated phosphodiesterases, which coincides with a decreased sensitivity to activation by calmodulin, results in decreased phosphodiesterase activity.
Beltman
J
J
Department of Pharmacology, University of Washington, Seattle 98195.
Sonnenburg
W K
WK
Beavo
J A
JA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology / Q000502:physiology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002147:Calmodulin / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D009928:Organ Specificity; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation
D002147:Calmodulin; D007527:Isoenzymes; D010750:Phosphoproteins; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases