Cyclic GMP-dependent Protein Kinase Signaling Pathway Inhibits RhoA-induced Ca2+ Sensitization of Contraction in Vascular Smooth Muscle*

By V. Sauzeau, Hélène Le Jeune, C. Cario‐Toumaniantz, A. Smolenski, S. Lohmann, J. Bertoglio, P. Chardin, P. Pacaud, G. Loirand. Journal of Biological Chemistry, 2000

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The potent vasodilator action of cyclic GMP-dependent protein kinase (cGK) involves decreasing the Ca2+ sensitivity of contraction of smooth muscle via stimulation of myosin light chain phosphatase through unknown mechanisms (Wu, X., Somlyo, A. V., and Somlyo, A. P. (1996)Biochem. Biophys. Res. Commun. 220, 658–663). Myosin light chain phosphatase activity is controlled by the small GTPase RhoA and its target Rho kinase. Here we demonstrate cGMP effects mediated by cGK that inhibit RhoA-dependent Ca2+ sensitization of contraction of blood vessels and actin cytoskeleton organization in cultured vascular myocytes. Ca2+ sensitization and actin organization were inhibited by both 8-bromo-cGMP and sodium nitroprusside (SNP). SNP also caused translocation of activated RhoA from the membrane to the cytosol. SNP-induced actin disassembly was lost in vascular myocytes in culture after successive passages but was restored by transfection of cells with cGK I. Furthermore, cGK phosphorylated RhoA in vitro, and addition of cGK I inhibited RhoA-induced Ca2+ sensitization in permeabilized smooth muscle. 8-Bromo-cGMP-induced actin disassembly was inhibited in vascular myocytes expressing RhoAAla-188, a mutant that could not be phosphorylated. Collectively, these results indicate that cGK phosphorylates and inhibits RhoA and suggest that the consequent inhibition of RhoA-induced Ca2+ sensitization and actin cytoskeleton organization contributes to the vasodilator action of nitric oxide.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/3fce7a8a4111faa9eba7b37ea6a83b7ba511d87e

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Citations in the corpus

The physiology and pathophysiology of nitric oxide in the brain. (2005, background): “This latter action can be modulated by a RhoA-dependent kinase (Rho kinase), which phosphorylates and inhibits the MLC phosphatase triggering contraction (Sauzeau et al., 2000).”