Signalling by cGMP-dependent protein kinases

Mol Cell Biochem. 1996 Apr 12-26;157(1-2):23-30. doi: 10.1007/BF00227877.

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) 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / physiology
  • Calcium / metabolism
  • Cyclic GMP / physiology
  • Cyclic GMP-Dependent Protein Kinases / chemistry
  • Cyclic GMP-Dependent Protein Kinases / genetics
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Endothelium, Vascular / physiology
  • Genetic Variation
  • Homeostasis
  • Humans
  • Ion Channels / physiology
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mammals
  • Models, Biological
  • Muscle Contraction
  • Muscle, Smooth / physiology
  • Nitric Oxide / physiology
  • Platelet Aggregation
  • Second Messenger Systems*
  • Signal Transduction*

Substances

  • Ion Channels
  • Isoenzymes
  • Nitric Oxide
  • Atrial Natriuretic Factor
  • Cyclic GMP-Dependent Protein Kinases
  • Cyclic GMP
  • Calcium