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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
1992-8-28
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pubmed:abstractText |
The aminoglycoside neomycin has recently been found to affect certain platelet-derived growth factor (PDGF) responses in C3H/10T1/2 C18 fibroblasts. Using porcine aortic endothelial cells transfected with PDGF alpha- or beta-receptors, we explored the possibility that neomycin interferes with the interaction between the different PDGF isoforms and their receptors. We found that neomycin (5 mM) inhibited the binding of 125I-PDGF-BB to the alpha-receptor with only partial effect on the binding of 125I-PDGF-AA; in contrast, the binding of 125I-PDGF-BB to the beta-receptor was not affected by the aminoglycoside. Scatchard analyses showed that neomycin (5 mM) decreased the number of binding sites for PDGF-BB on alpha-receptor-expressing cells by 87%. Together with cross-competition studies with 125I-labeled PDGF homodimers, the effect of neomycin indicates that PDGF-AA and PDGF-BB bind to both common and unique structures on the PDGF alpha-receptor. Neomycin specifically inhibited the autophosphorylation of the alpha-receptor by PDGF-BB, with less effect on the phosphorylation induced by PDGF-AA and no effect on the phosphorylation of the beta-receptor by PDGF-BB. Thus, neomycin is a PDGF isoform- and receptor-specific antagonist that provides a possibility to compare the signal transduction pathways of alpha- and beta-receptors in cells expressing both receptor types. This approach was used to show that activation of PDGF beta-receptors by PDGF-BB mediated a chemotactic response in human fibroblasts, whereas activation of alpha-receptors by the same ligand inhibited chemotaxis.
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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/Aminoglycosides,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Neomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
267
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15635-41
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:1322402-Aminoglycosides,
pubmed-meshheading:1322402-Animals,
pubmed-meshheading:1322402-Antibodies,
pubmed-meshheading:1322402-Binding, Competitive,
pubmed-meshheading:1322402-Cell Line,
pubmed-meshheading:1322402-Chemotaxis,
pubmed-meshheading:1322402-Endothelium, Vascular,
pubmed-meshheading:1322402-Humans,
pubmed-meshheading:1322402-Kinetics,
pubmed-meshheading:1322402-Mice,
pubmed-meshheading:1322402-Models, Biological,
pubmed-meshheading:1322402-Neomycin,
pubmed-meshheading:1322402-Platelet-Derived Growth Factor,
pubmed-meshheading:1322402-Receptors, Cell Surface,
pubmed-meshheading:1322402-Receptors, Platelet-Derived Growth Factor,
pubmed-meshheading:1322402-Recombinant Proteins,
pubmed-meshheading:1322402-Swine,
pubmed-meshheading:1322402-Transfection
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pubmed:year |
1992
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pubmed:articleTitle |
Neomycin is a platelet-derived growth factor (PDGF) antagonist that allows discrimination of PDGF alpha- and beta-receptor signals in cells expressing both receptor types.
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pubmed:affiliation |
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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