Diversity of calcium action in regulation of mammalian calmodulin-dependent cyclic nucleotide phosphodiesterase.
Calmodulin(CaM)-dependent cyclic nucleotide phosphodiesterase (PDE1) plays a critical role in the complex interactions between the cyclic nucleotide and Ca(2+) second messenger systems. Bovine brain contains two major PDE1 isozymes, designated according to tissue origin and subunit molecular mass as brain 60 kDa and 63 kDa PDE1 isozymes. Kinetic properties suggest that 63 kDa PDE1 isozyme is distinct from 60 kDa, heart and lung PDE1 isozymes. Although 60 kDa, heart and lung PDE1 isozymes are almost identical in immunological properties, they are differentially activated by calmodulin (CaM). These isozymes are further distinguished by the effects of pharmacological agents. Another main difference is that 60 kDa PDE1 isozyme is a substrate of cAMP-dependent protein kinase, whereas, 63 kDa PDE1 isozyme is phosphorylated by CaM-dependent protein kinase. The phosphorylation of PDE1 isozymes is accompanied by a decrease in the isozyme affinity towards CaM, and it can be reversed by a CaM-dependent phosphatase (calcineurin). The complex regulatory properties of PDE1 isozymes are precisely regulated by cross-talk between the Ca(2+) and cAMP signaling pathways.
Department of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, SK Canada S7N 4H4. rsharma@scf.sk.ca
Rajendra K
RK
Sharma
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D015290:Second Messenger Systems
D002147:Calmodulin; D000242:Cyclic AMP; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D002118:Calcium