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

Sauzeau, Vincent; Jeune, Hélène Le; Cario‐Toumaniantz, Chrystelle; Smolenski, Albert; Lohmann, Suzanne M.; Bertoglio, Jacques; Chardin, Pierre Teilhard de; Pacaud, Pierre; Loirand, Gervaise

doi:10.1074/jbc.m000753200

Cited by 561 publications

(520 citation statements)

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“…Here both cAMP-increasing agent and cGMP-increasing agent inhibited the association between PLD1 and Val14RhoA, although the possible physiological role of PKG in PLD signaling is unknown. This result indicates that RhoA phosphorylation by cAMP and cGMP may affect binding of RhoA to PLD1, since PKA and PKG phosphorylate serine188 on RhoA (Lang et al, 1996;Sauzeau et al, 2000;Sawada et al, 2001;Ellerbroek et al, 2003). Moreover, consistent with our findings, PKA-mediated phosphorylation decreased the binding of RhoA to another downstream effector molecule, Rho (Dong et al, 1998).…”

Section: Discussionsupporting

confidence: 80%

“…To determine whether intracellular cAMP levels regulate the association between PLD1 and the active form of RhoA, RhoA was immunoprecipitated from cells treated with or without dbcAMP and the amount of co-precipitated PLD1 was measured. RhoA was reported to be phosphorylated at Ser188 by both PKA and PKG (Lang et al, 1996;Kwak and Uhlinger, 2000;Sauzeau et al, 2000;Sawada et al, 2001). dbcAMP or dbcGMP induced a marked increase in the phosphorylation of band co-localized with the immunodetected band of Val14-RhoA ( Figure 4B).…”

Section: Effect Of Phosphorylation On the Interaction Betw Een Pld1 Amentioning

confidence: 97%

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Phosphorylation of phospholipase D1 and the modulation of its interaction with RhoA by cAMP-dependent protein kinase

Jang

Lee²,

Park³

et al. 2004

Exp Mol Med

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A bstractAgents that elevate cellular cAM P are know n to inhibit the activation of phospholipase D (PLD). W e investigated w hether PLD can be phosphorylated by cAM P-dependent protein kinase (PKA) and PKA-m ediated phosphorylation affects the interaction betw een PLD and RhoA, a m em brane regulator of PLD. PLD1, but not PLD2 w as found to be phosphorylated in vivo by the treatm ent of dibutyryl cA M P (dbcA M P) and in vitro by PKA. PKA inhibitor (KT5720) abolished the dbcAM P-induced phosphorylation of PLD1, but dibutyryl cGMP (dbcGMP) failed to phosphorylate PLD1. The association betw een PLD1 and Val14RhoA in an im m unoprecipitation assay w as abolished by both dbcAM P and dbcG M P. M oreover, RhoA but not PLD1 w as dissociated from the m em brane to the cytosolic fraction in dbcAM P-treated cells. These results suggest that both PLD1 and RhoA are phosphorylated by PKA and the interaction betw een PLD1 and RhoA is inhibited by the phosphorylation of RhoA rather than by the phosphorylation of PLD1.

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Section: Discussionsupporting

confidence: 80%

Section: Effect Of Phosphorylation On the Interaction Betw Een Pld1 Amentioning

confidence: 97%

Phosphorylation of phospholipase D1 and the modulation of its interaction with RhoA by cAMP-dependent protein kinase

Jang

Lee²,

Park³

et al. 2004

Exp Mol Med

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“…On the other hand, several investigators have shown that NO blocks the migration of RhoA from the cytosol to the membrane, thereby inhibiting the RhoA/ROCK signaling pathway. 114,115 It is thought that there is an interaction between activated ROCK and endothelial dysfunction in human vessels. Indeed, we have confirmed that hypertension is associated with both endothelial dysfunction and increased ROCK activity, and that endothelial dysfunction and increased ROCK activity are simultaneously improved by an aldosterone blocker in patients with hypertension.…”

Section: Tetrahydrobiopterin (Bh 4 )mentioning

confidence: 99%

Endothelial dysfunction and hypertension in aging

2012

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Hypertension is one of the common diseases in the elderly. The prevalence of hypertension markedly increases with advancing age. Both aging and hypertension have a critical role in cardiovascular and cerebrovascular complications. Although aging and hypertension, either independently or collectively, impair endothelial function, aging and hypertension may have similar cascades for the pathogenesis and development of endothelial dysfunction. Nitric oxide (NO) has an important role in regulation of vascular tone. Decrease in NO bioavailability by endothelial dysfunction would lead to elevation of blood pressure. An imbalance of reduced production of NO or increased production of reactive oxygen species, mainly superoxide, may promote endothelial dysfunction. One possible mechanism by which the prevalence of hypertension is increased in relation to aging may be advancing endothelial dysfunction associated with aging through an increase in oxidative stress. In addition, endothelial cell senescence is also involved in aging-related endothelial dysfunction. In this review, we focus on recent findings and interactions between endothelial function, oxidative stress and hypertension in aging.

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“…(kinase-related protein of 17kDa), which has a similar amino acid sequence as myosin light chain kinase (MLCK) at COOH terminal with 156 amino acid, and promotes the dephosphorylation of myosin light chain 20 (MLC20), which is closed associated with the calcium sensitization 6 . The previous studies showed that PKG was involved in the calcium desensitization of vascular smooth muscle after hemorrhagic shock, which was possibly related to MLCK 3,7 .…”

Section: Protein Kinase G (Pkg) May Phosphorylate Telokinmentioning

confidence: 99%

Role of protein kinase G on the post-shock mesenteric lymph blockage ameliorating vascular calcium sensitivity

et al. 2013

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PURPOSE:To investigate the role of protein kinase G (PKG) in blocking post-shock mesenteric lymph (PSML) return ameliorating the calcium sensitivity in hemorrhagic shock rats. METHODS:Male Wistar rats were randomly divided into sham, shock, shock+ligation (shock plus mesenteric lymph duct ligation (MLDL)), shock+drainage (shock plus PSML drainage) groups. After shock (hypotension 40mmHg) for three hours or corresponding times, the superior mesenteric artery (SMA) was taken out for detecting the PKG and phospho PKG (p-PKG) contents, and the vascular rings of SMA were prepared for assaying the calcium sensitivity using an isolated organ perfusion system. RESULTS:The PKG and p-PKG contents of SMA in shock group were significantly increased than that of sham group, and MLDL or PSML drainage reducing the levels of PKG and p-PKG. Meanwhile, the vascular calcium sensitivity in shock group was significantly lower than that of sham group, MLDL or PSML drainage enhanced the calcium sensitivity. After incubating with PKG regulators in shock+ligation and shock+drainage groups, the PKG agonist 8Br-cGMP reduced the contractility of vascular rings to gradient calcium ions and Emax and the PKG inhibitor agonist KT5823 elevated the calcium sensitivity significantly. CONCLUSION:Protein kinase G plays an important role in post-shock mesenteric lymph blockage improving vascular calcium sensitivity.

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

Abstract: The potent vasodilator action of cyclic GMP-dependent protein kinase (cGK) involves decreasing the Ca

Cited by 561 publications

References 40 publications

Phosphorylation of phospholipase D1 and the modulation of its interaction with RhoA by cAMP-dependent protein kinase

Phosphorylation of phospholipase D1 and the modulation of its interaction with RhoA by cAMP-dependent protein kinase

Endothelial dysfunction and hypertension in aging

Role of protein kinase G on the post-shock mesenteric lymph blockage ameliorating vascular calcium sensitivity

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