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

@article{Sauzeau2000CyclicGP,
  title={Cyclic GMP-dependent Protein Kinase Signaling Pathway Inhibits RhoA-induced Ca2+ Sensitization of Contraction in Vascular Smooth Muscle*},
  author={Vincent Sauzeau and Hélène Le Jeune and Chrystelle Cario-Toumaniantz and Albert Smolenski and Suzanne M. Lohmann and Jacques Bertoglio and Pierre Chardin and Pierre Pacaud and Gervaise Loirand},
  journal={The Journal of Biological Chemistry},
  year={2000},
  volume={275},
  pages={21722 - 21729}
}
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… 

Figures and Tables from this paper

Actions Downstream of Cyclic GMP/Protein Kinase G Can Reverse Protein Kinase C-mediated Phosphorylation of CPI-17 and Ca2+Sensitization in Smooth Muscle*

TLDR
It is concluded that actions downstream of cGMP/PKG can reverse PKC-mediated phosphorylation of CPI-17 and Ca2+ sensitization in smooth muscle.

Negative regulation of rho signaling by insulin and its impact on actin cytoskeleton organization in vascular smooth muscle cells: role of nitric oxide and cyclic guanosine monophosphate signaling pathways.

TLDR
It is concluded that insulin may inhibit Rho signaling by affecting posttranslational modification of RhoA via nitric oxide/cGMP signaling pathway to cause MBP activation, actin cytoskeletal disorganization, and vasodilation.

Modulation of Ca2+ Sensitivity by Cyclic Nucleotides in Smooth Muscle from Protein Kinase G-deficient Mice*

TLDR
The results show that PKG is the main target for cGMP-induced relaxation in intestinal smooth muscle, and PKG-independent pathways are activated at 1000-fold higher cG MP concentrations.

Nitric Oxide Induces Dilation of Rat Aorta via Inhibition of Rho-Kinase Signaling

TLDR
The hypothesis that endogenous NO-mediated vasodilation occurs through the inhibition of Rho-kinase constrictor activity in the intact rat aorta is supported.

Cyclic guanosine monophosphate-dependent protein kinase I promotes adhesion of primary vascular smooth muscle cells.

TLDR
The results identify a novel proadhesive function of cGMP/cGKI signaling in primary VSMCs and suggest that the opposing effects of this pathway on VSMC number depend on the phenotypic context of the cells.

Inhibition of MLC20 Phosphorylation Downstream of Ca2+ and RhoA: A Novel Mechanism Involving Phosphorylation of Myosin Phosphatase Interacting Protein (M-RIP) by PKG and Stimulation of MLC Phosphatase Activity

TLDR
Evidence is provided that PKG induces phosphorylation of M-RIP and enhances its association with MYPT1 to augment MLCP activity and MLC20 dephosphorylation and inhibits muscle contraction, downstream of Ca2+- or RhoA-dependent pathways.

Direct Binding and Regulation of RhoA Protein by Cyclic GMP-dependent Protein Kinase Iα*

TLDR
RhoA is identified as a target of activated PKGIα and shows further that PKGI α binds directly to RhoA, inhibiting its activation and translocation, and that direct binding of activatedPKGIα to RHoA is central to cGMP-mediated inhibition of the VSMC Rho kinase contractile pathway.

Ca2+-Independent, Inhibitory Effects of Cyclic Adenosine 5′-Monophosphate on Ca2+ Regulation of Phosphoinositide 3-Kinase C2α, Rho, and Myosin Phosphatase in Vascular Smooth Muscle

TLDR
Observations indicate that cAMP inhibits Ca2-mediated activation of the MLCP-regulating signaling pathway comprising PI3K-C2α, Rho, and Rho kinase in a manner independent of Ca2+ and point to the novel mechanism of the cAMP actions in the regulation of vascular smooth muscle contraction.

K+-Induced Smooth Muscle Calcium Sensitization Requires RhoA Kinase (ROK) Translocation to Caveolae Which Is Inhibited in Non-Neuronal Cell Memory

TLDR
The data support the hypothesis that the information storage method utilized in non-neuronal cell memory involves an inhibition of the RhoA/ROK pathway, and suggest that the membranous location of caveolae is an important factor in Rho a/Rok-mediated Ca2+-sensitization.

The cyclic GMP‐protein kinase G pathway regulates cytoskeleton dynamics and motility in astrocytes

TLDR
It is demonstrated that NO‐dependent cGMP formation is involved in the morphological change induced by lipopolysaccharide (LPS) in cultured rat cerebellar astroglia, indicating that cG MP‐mediated pathways may regulate physio‐pathologically relevant responses in astroglial cells.
...

References

SHOWING 1-10 OF 39 REFERENCES

Cyclic GMP Causes Ca2+ Desensitization in Vascular Smooth Muscle by Activating the Myosin Light Chain Phosphatase*

TLDR
The results of this study strongly suggest that cGMP indirectly activates light chain phosphatase, the first proposed mechanism for cBromo-cGMP-induced Ca2+ desensitization in vasodilatation.

Rho and Rho kinase mediate thrombin-stimulated vascular smooth muscle cell DNA synthesis and migration.

TLDR
Thrombin activates Rho in RASMCs and Rho is established as a critical mediator of thrombin receptor effects on DNA synthesis and cell migration in these cells.

Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes.

TLDR
It is demonstrated here that cAMP‐dependent protein kinase A (PKA) phosphorylates RhoA in its C‐terminal region, on serine residue 188, and this phosphorylation supports the existence of an alternative pathway for terminating RHoA signalling whereby GTP‐bound Rho a, when phosphorylated, could be separated from its putative effector(s) independently of its GTP/GDP cycling.

Cyclic GMP-dependent stimulation reverses G-protein-coupled inhibition of smooth muscle myosin light chain phosphate.

TLDR
It is concluded that cyclic GMP-dependent kinase, activated by 8-br-cGMP, increases smooth muscle myosin light chain phosphatase activity and counteracts the inhibition of the latter enzyme by G-protein(s).

cAMP-induced Morphological Changes Are Counteracted by the Activated RhoA Small GTPase and the Rho Kinase ROKα*

TLDR
It is demonstrated that RhoAV14A188, which cannot be phosphorylated by PKA in vitro, is more effective than Rho AV14 in preventing cells from responding to cAMP and in inducing actin stress fiber formation, suggesting that cAMP-mediated down-regulation of RhoA binding to its effector ROKα may be involved in this antagonism.

The Rho‐related protein Rnd1 inhibits Ca2+ sensitization of rat smooth muscle

TLDR
Rnd1 inhibits agonist‐ and GTPγS‐induced Ca2+ sensitization of smooth muscle by specifically interfering with a RhoA‐dependent mechanism and an increase in Rnd1 expression may account, at least in part, for the steroid‐induced decrease in agonists' Ca2- sensitization.

Regulation of intracellular Ca2+ levels in cultured vascular smooth muscle cells. Reduction of Ca2+ by atriopeptin and 8-bromo-cyclic GMP is mediated by cyclic GMP-dependent protein kinase.

TLDR
It is suggested that repetitively passaged cultured rat aortic smooth muscle cells lose their responsiveness to cGMP concurrently with the loss of cG MP-dependent protein kinase, and restoration of kinase to the cells results in the restoration of responsiveness tocGMP.

Role of guanine nucleotide-binding proteins--ras-family or trimeric proteins or both--in Ca2+ sensitization of smooth muscle.

  • M. GongK. Iizuka A. Somlyo
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
TLDR
It is concluded that p21rho may play a role in physiological Ca2+ sensitization as a cofactor with other messengers, rather than as a sole direct inhibitor of smooth muscle MLC20 phosphatase.

Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha.

TLDR
Un Uncoupling of the cGKIalpha-MBS interaction prevents cGMP-dependent dephosphorylation of myosin light chain, demonstrating that this interaction is essential to the regulation of vascular smooth muscle cell tone.

Defective smooth muscle regulation in cGMP kinase I‐deficient mice

TLDR
It is shown that cAMP and cGMP signal via independent pathways, with cGKI being the specific mediator of the NO/cGMP effects in murine smooth muscle.