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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1992-12-9
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pubmed:abstractText |
Agonist binding to guanine nucleotide-binding protein (G protein)-coupled receptors in membranes of myeloid differentiated human leukemia (HL-60) cells is inhibited by guanine nucleotides, most potently by the GTP analog guanosine 5'-(gamma-thio)triphosphate (GTP gamma S). In order to study whether GTP gamma S formed locally from adenosine 5'-(gamma-thio)triphosphate (ATP gamma S) and GDP by nucleoside diphosphokinase has any advantage over exogenously added GTP gamma S in binding to and activating G proteins, regulation of complement component 5a (C5a) binding to its receptors, as well as formation of GTP gamma S, was studied in membranes of HL-60 cells. GTP gamma S added to HL-60 membranes potently inhibited binding of 125I-C5a (IC50 about 3 nM), an effect not influenced by addition of either GDP or ATP gamma S. When HL-60 membranes were incubated with the combination of ATP gamma S and GDP, a marked potentiation (up to 300-fold) of the inhibition caused by either GDP or ATP gamma S alone was observed. By measuring nucleoside diphosphokinase-catalyzed formation of GTP gamma S and inhibition of 125I-C5a binding in the presence of GDP and ATP gamma S under identical assay conditions, it was found that formed GTP gamma S inhibited binding of 125I-C5a with an IC50 value of about 0.3 nM, thus being about 10-fold more potent than exogenously added GTP gamma S. These data suggest that the GTP gamma S-forming nucleoside diphosphokinase is closely associated with the C5a receptor-G protein complex and channels the formed GTP gamma S into the G protein.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C5a,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Nucleoside-Diphosphate Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/adenosine 5'-O-(3-thiotriphosphate)
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
731-5
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1331759-Adenosine Triphosphate,
pubmed-meshheading:1331759-Cells, Cultured,
pubmed-meshheading:1331759-Complement C5a,
pubmed-meshheading:1331759-GTP-Binding Proteins,
pubmed-meshheading:1331759-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:1331759-Humans,
pubmed-meshheading:1331759-Nucleoside-Diphosphate Kinase
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pubmed:year |
1992
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pubmed:articleTitle |
Evidence for nucleoside diphosphokinase-dependent channeling of guanosine 5'-(gamma-thio)triphosphate to guanine nucleotide-binding proteins.
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pubmed:affiliation |
Institut für Pharmakologie, Universität GH Essen, FRG.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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