Source:http://linkedlifedata.com/resource/pubmed/id/11359779
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
30
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| pubmed:dateCreated |
2001-7-23
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| pubmed:abstractText |
Here we provide evidence to show that the platelet-derived growth factor beta receptor is tethered to endogenous G-protein-coupled receptor(s) in human embryonic kidney 293 cells. The tethered receptor complex provides a platform on which receptor tyrosine kinase and G-protein-coupled receptor signals can be integrated to produce more efficient stimulation of the p42/p44 mitogen-activated protein kinase pathway. This was based on several lines of evidence. First, we have shown that pertussis toxin (which uncouples G-protein-coupled receptors from inhibitory G-proteins) reduced the platelet-derived growth factor stimulation of p42/p44 mitogen-activated protein kinase. Second, transfection of cells with inhibitory G-protein alpha subunit increased the activation of p42/p44 mitogen-activated protein kinase by platelet-derived growth factor. Third, platelet-derived growth factor stimulated the tyrosine phosphorylation of the inhibitory G-protein alpha subunit, which was blocked by the platelet-derived growth factor kinase inhibitor, tyrphostin AG 1296. We have also shown that the platelet-derived growth factor beta receptor forms a tethered complex with Myc-tagged endothelial differentiation gene 1 (a G-protein-coupled receptor whose agonist is sphingosine 1-phosphate) in cells co-transfected with these receptors. This facilitates platelet-derived growth factor-stimulated tyrosine phosphorylation of the inhibitory G-protein alpha subunit and increases p42/p44 mitogen-activated protein kinase activation. In addition, we found that G-protein-coupled receptor kinase 2 and beta-arrestin I can associate with the platelet-derived growth factor beta receptor. These proteins play an important role in regulating endocytosis of G-protein-coupled receptor signal complexes, which is required for activation of p42/p44 mitogen-activated protein kinase. Thus, platelet-derived growth factor beta receptor signaling may be initiated by G-protein-coupled receptor kinase 2/beta-arrestin I that has been recruited to the platelet-derived growth factor beta receptor by its tethering to a G-protein-coupled receptor(s). These results provide a model that may account for the co-mitogenic effect of certain G-protein-coupled receptor agonists with platelet-derived growth factor on DNA synthesis.
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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/6,7-dimethoxy-3-phenylquinoxaline,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella,
http://linkedlifedata.com/resource/pubmed/chemical/sphingosine 1-phosphate
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
27
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| pubmed:volume |
276
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
28578-85
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11359779-Cell Line,
pubmed-meshheading:11359779-Cells, Cultured,
pubmed-meshheading:11359779-Dose-Response Relationship, Drug,
pubmed-meshheading:11359779-Enzyme Activation,
pubmed-meshheading:11359779-Enzyme Inhibitors,
pubmed-meshheading:11359779-Humans,
pubmed-meshheading:11359779-Lysophospholipids,
pubmed-meshheading:11359779-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:11359779-Pertussis Toxin,
pubmed-meshheading:11359779-Phosphorylation,
pubmed-meshheading:11359779-Platelet-Derived Growth Factor,
pubmed-meshheading:11359779-Precipitin Tests,
pubmed-meshheading:11359779-Protein Binding,
pubmed-meshheading:11359779-Receptor, Platelet-Derived Growth Factor beta,
pubmed-meshheading:11359779-Receptors, Cell Surface,
pubmed-meshheading:11359779-Recombinant Proteins,
pubmed-meshheading:11359779-Signal Transduction,
pubmed-meshheading:11359779-Sphingosine,
pubmed-meshheading:11359779-Transfection,
pubmed-meshheading:11359779-Tyrphostins,
pubmed-meshheading:11359779-Virulence Factors, Bordetella
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| pubmed:year |
2001
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| pubmed:articleTitle |
Tethering of the platelet-derived growth factor beta receptor to G-protein-coupled receptors. A novel platform for integrative signaling by these receptor classes in mammalian cells.
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| pubmed:affiliation |
Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor St., Glasgow, G4 0NR, Scotland, United Kingdom.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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