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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1992-12-18
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pubmed:abstractText |
The ability of activators of the beta-adrenergic receptor to elevate intracellular cAMP levels in murine fibroblasts is enhanced upon overexpression of avian c-src [Bushman et al. (1990) Proc. natn. Acad. Sci. U.S.A. 87, 7462-7466]. To investigate the molecular basis for this effect, we prepared particulate fractions from control and pp60c-src overexpressing C3H10T1/2 fibroblasts and assessed the relative abilities of several activators of the beta-adrenergic receptor-Gs-adenylyl cyclase (AC) signal transduction pathway to stimulate the enzymatic response. Two- to three-fold increases in both the sensitivity and maximum responsiveness of AC to the beta-adrenergic agonist isoproterenol were consistently observed in fractions prepared from the c-src overexpressing cells. Interestingly, the AC response to two agents believed to act directly at the level of the G protein were either enhanced (NaF) or unaffected (GTP gamma S) by c-src overexpression. Finally, overexpression of c-src was associated with a reduced ability of both Mn2+ and forskolin to activate AC directly. These results suggest that overexpression of wild type c-src may affect two distinct steps in the regulation of AC exerting a positive effect at the level of Gs activation and a negative effect on AC itself. As no differences in the relative number or affinity of beta-adrenergic receptors, or in the level of AC, Gs alpha or G beta, were detected between control cells and those overexpressing c-src, we propose that pp60c-src overexpression results in a modification of one or more components in this signal transduction pathway.
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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/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins pp60(c-src),
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0898-6568
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
531-41
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:1384635-Adenylate Cyclase,
pubmed-meshheading:1384635-Animals,
pubmed-meshheading:1384635-Cell Line,
pubmed-meshheading:1384635-Cyclic AMP,
pubmed-meshheading:1384635-Enzyme Activation,
pubmed-meshheading:1384635-GTP-Binding Proteins,
pubmed-meshheading:1384635-Isoproterenol,
pubmed-meshheading:1384635-Mice,
pubmed-meshheading:1384635-Proto-Oncogene Proteins pp60(c-src),
pubmed-meshheading:1384635-Receptors, Adrenergic, beta,
pubmed-meshheading:1384635-Signal Transduction
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pubmed:year |
1992
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pubmed:articleTitle |
Overexpression of pp60c-src is associated with altered regulation of adenylyl cyclase.
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pubmed:affiliation |
Glaxo Research Institute, Department of Cell Biology, Research Triangle Park, NC 27709.
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pubmed:publicationType |
Journal Article
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