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Signalling by cGMP-dependent protein kinases

  • Part I: Basic Mechanisms
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Abstract

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) cGMPgated 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 α and a β 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.

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  1. Department of Biochemistry, Cardiovascular Research Institute COEUR, Medical Faculty, Erasmus University Rotterdam, P.O. Box 1738, 3000, DR Rotterdam, The Netherlands

    Arie B. Vaandrager & Hugo R. de Jonge

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  1. Arie B. Vaandrager
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  2. Hugo R. de Jonge
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Vaandrager, A.B., de Jonge, H.R. Signalling by cGMP-dependent protein kinases. Mol Cell Biochem 157, 23–30 (1996). https://doi.org/10.1007/BF00227877

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