Linked Life Data

15774480

Source:http://linkedlifedata.com/resource/pubmed/id/15774480

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2005-5-17
pubmed:abstractText
The endothelial isoform of nitric-oxide synthase (eNOS) is regulated by a complex pattern of post-translational modifications. In these studies, we show that eNOS is dynamically regulated by S-nitrosylation, the covalent adduction of nitric oxide (NO)-derived nitrosyl groups to the cysteine thiols of proteins. We report that eNOS is tonically S-nitrosylated in resting bovine aortic endothelial cells and that the enzyme undergoes rapid transient denitrosylation after addition of the eNOS agonist, vascular endothelial growth factor. eNOS is thereafter progressively renitrosylated to basal levels. The receptor-mediated decrease in eNOS S-nitrosylation is inversely related to enzyme phosphorylation at Ser(1179), a site associated with eNOS activation. We also document that targeting of eNOS to the cell membrane is required for eNOS S-nitrosylation. Acylation-deficient mutant eNOS, which is targeted to the cytosol, does not undergo S-nitrosylation. Using purified eNOS, we show that eNOS S-nitrosylation by exogenous NO donors inhibits enzyme activity and that eNOS inhibition is reversed by denitrosylation. We determine that the cysteines of the zinc-tetrathiolate that comprise the eNOS dimer interface are the targets of S-nitrosylation. Mutation of the zinc-tetrathiolate cysteines eliminates eNOS S-nitrosylation but does not eliminate NO synthase activity, arguing strongly that disruption of the zinc-tetrathiolate does not necessarily lead to eNOS monomerization in vivo. Taken together, these studies suggest that eNOS S-nitrosylation may represent an important mechanism for regulation of NO signaling pathways in the vascular wall.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19888-94
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15774480-Amino Acid Substitution, pubmed-meshheading:15774480-Animals, pubmed-meshheading:15774480-Base Sequence, pubmed-meshheading:15774480-Cattle, pubmed-meshheading:15774480-Cells, Cultured, pubmed-meshheading:15774480-DNA, Complementary, pubmed-meshheading:15774480-Endothelium, Vascular, pubmed-meshheading:15774480-Insulin, pubmed-meshheading:15774480-Mutagenesis, Site-Directed, pubmed-meshheading:15774480-Nitric Oxide, pubmed-meshheading:15774480-Nitric Oxide Synthase, pubmed-meshheading:15774480-Nitric Oxide Synthase Type III, pubmed-meshheading:15774480-Protein Processing, Post-Translational, pubmed-meshheading:15774480-Receptors, Cell Surface, pubmed-meshheading:15774480-Recombinant Proteins, pubmed-meshheading:15774480-Signal Transduction, pubmed-meshheading:15774480-Transfection, pubmed-meshheading:15774480-Vascular Endothelial Growth Factor A
pubmed:year
2005
pubmed:articleTitle
Receptor-regulated dynamic S-nitrosylation of endothelial nitric-oxide synthase in vascular endothelial cells.
pubmed:affiliation
Cardiovascular, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural