Linked Life Data

15890975

Source:http://linkedlifedata.com/resource/pubmed/id/15890975

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-6-10
pubmed:abstractText
cAMP and cyclic GMP-dependent kinases (PKA and PKG) phosphorylate the small G protein RhoA on Ser188. We have previously demonstrated that phosphorylation of Ser188 inhibits RhoA-dependent functions and positively regulates RhoA expression, and that the nitric oxide (NO)/cGMP-dependent protein kinase pathway plays an essential role, both in vitro and in vivo, in the regulation of RhoA protein expression and functions in vascular smooth muscle cells. Here we analyze the consequences of Ser188 phosphorylation on RhoA protein degradation. By expressing Ser188 phosphomimetic wild-type (WT-RhoA-S188E) and active RhoA proteins (Q63L-RhoA-S188E), we show that phosphorylation of Ser188 of RhoA protects RhoA, particularly its active form, from ubiquitin-mediated proteasomal degradation. Coimmunoprecipitation experiments indicate that the resistance of the phosphorylated active form of RhoA to proteasome-mediated degradation is because of its cytoplasmic sequestration through enhanced RhoGDI interaction. In rat aortic smooth muscle cells, stimulation of PKG and inhibition of proteasome by lactacystin, induce nonadditive increases in RhoA protein expression. In addition, stimulation of PKG leads to the accumulation of GTP-bound RhoA in the cytoplasm. In vivo stimulation of the NO/PKG signaling by treating rats with sildenafil increased RhoA level and RhoA phosphorylation, and enhanced its association to RhoGDI in the pulmonary artery, whereas opposite effects are induced by chronic inhibition of NO synthesis in N-omega-nitro-L-arginine-treated rats. Our results thus suggest that Ser188 phosphorylation-mediated protection against degradation is a physiological process regulating the level of endogenous RhoA and define a novel function for RhoGDI, as an inhibitor of Rho protein degradation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1152-60
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15890975-Animals, pubmed-meshheading:15890975-Cells, Cultured, pubmed-meshheading:15890975-Cyclic GMP-Dependent Protein Kinases, pubmed-meshheading:15890975-Cytosol, pubmed-meshheading:15890975-Guanine Nucleotide Dissociation Inhibitors, pubmed-meshheading:15890975-Humans, pubmed-meshheading:15890975-Male, pubmed-meshheading:15890975-Mice, pubmed-meshheading:15890975-Muscle, Smooth, Vascular, pubmed-meshheading:15890975-Nitric Oxide, pubmed-meshheading:15890975-Phosphorylation, pubmed-meshheading:15890975-Proteasome Endopeptidase Complex, pubmed-meshheading:15890975-Rats, pubmed-meshheading:15890975-Rats, Wistar, pubmed-meshheading:15890975-Serine, pubmed-meshheading:15890975-Signal Transduction, pubmed-meshheading:15890975-Swiss 3T3 Cells, pubmed-meshheading:15890975-Ubiquitin, pubmed-meshheading:15890975-rhoA GTP-Binding Protein
pubmed:year
2005
pubmed:articleTitle
Phosphorylation of serine 188 protects RhoA from ubiquitin/proteasome-mediated degradation in vascular smooth muscle cells.
pubmed:affiliation
INSERM U-533, Faculté des Sciences, 2 rue de la Houssinière, BP 92208, 44322 Nantes cedex 3, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't