Signalling by cGMP-dependent protein kinases.
The second messenger cGMP is a major intracellular mediator of the vaso-active agents nitric oxide and natriuretic peptides. The principal targets of cGMP are (i) phosphodiesterases, resulting in interference with the cAMP-signalling pathway, (ii) cGMP-gated cation channels, and (iii) cGMP-dependent protein kinases (cGKs). Only two mammalian isotypes of cGK have been described so far: type I cGK, consisting of an alpha and a beta isoform, presumably splice variants of a single gene, and identified as the most prominent cGK isotype in the cardio-vascular system; and type II cGK, expressed mainly in the intestine, the kidney and the brain. High levels of cGK I are found in vascular smooth muscle cells, endothelial cells and platelets. In these cells, cGK I is thought to counteract the increase in contraction provoked by Ca-mobilizing agonists, to reduce endothelial permeability and to inhibit platelet aggregation, respectively. Relatively low levels of cGK I are found in cardiomyocytes. In this cell type, cGK is implicated in the negative inotropic effect of cGMP, presumably through modulation of Ca channels and by diminishing the Ca-sensitivity of contractile proteins.
Vaandrager
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Department of Biochemistry, Cardiovascular Research Institute COEUR, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
de Jonge
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D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology; D014644:Genetic Variation; D006706:Homeostasis; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008322:Mammals; D008954:Models, Biological; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010974:Platelet Aggregation; D015290:Second Messenger Systems; D015398:Signal Transduction
D007473:Ion Channels; D007527:Isoenzymes; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D002118:Calcium