Role of cGMP dependent protein kinases in the circadian system

cGMP-dependent protein kinase(PKG) is the major intracellular receptor for cyclic guanosine monophosphate(cGMP).Two forms of PKG,PKG-I and PKG-II,occur in mammalian tissues.PKG may mediate nitric oxide-cGMP-induced vasodilation through decreasing intracellular calcium concentration by the activation of calcium-activated potassium channel on the cell membrane and phosphorylation of phospholamban(PLB) and IP_3 receptor-associated PKG-I substrate(IRAG) on the sarcoplasmic reticulum.PKG may also decrease the sensitivity of myosin to calcium by stimulating the activity of myosin light chain phosphatase and by inhibiting Rho kinase activity.PKG plays an important role in regulating the gene expression,phenotype,and proliferation of vascular smooth muscle cells.PKG activation inhibits platelet aggregation and myocardial hypertrophy.Recent studies indicate that the alternations of PKG expression and activity are closely related with the pathogenesis of atherosclerosis,restenosis,hypertension,hyperlipemia as well as nitrate tolerance.