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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-4-1
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pubmed:abstractText |
Cyclic AMP-dependent induction of differentiation by activation of the beta-adrenergic receptor is correlated with inhibition of protein kinase B activity concomitant with growth arrest and increase in glial fibrillary acidic protein (GFAP) synthesis in rat C6 glioma cells. Costimulation of the beta-adrenergic receptor with purinergic receptors activated by 2-methylthio-adenosine-5'-diphosphate (2MeSADP) increased protein kinase B (PKB) phosphorylation above the level measured in non-stimulated cells and abolished cAMP-dependent differentiation. Transfection of cells with constitutively active PKB confirmed that reactivation of PKB is involved in the 2MeSADP-dependent inhibition of GFAP synthesis. The P2Y(12) and P2Y(13) receptor antagonist AR-C69931MX [N(6)-(2-methylthioethyl)-2-(3,3,3-trifluoropropylthio)-beta,gamma-dichloro-methylene ATP] decreased PKB phosphorylation to the level in non-stimulated cells, whereas the P2Y(13) antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) and P(1),P(3)-di(adenosine-5') tetraphosphate (Ap(4)A) did not alter the 2MeSADP-induced phosphorylation of PKB, showing that enhanced PKB activity and subsequent phosphorylation of glycogen synthase kinase-3 is due to stimulation of the P2Y(12) receptor. In addition, experiments in the presence of pertussis toxin and phosphatidylinositol 3-kinase (PI 3-K) activity assays demonstrated that the P2Y(12) receptor-mediated increase in PKB phosphorylation is G(i) protein- and PI 3-K-dependent. The presented data demonstrated that a cAMP-dependent inhibition of PKB induces differentiation of C6 glioma cells and that inhibition of adenylate cyclase and reactivation of the PI 3-K/PKB pathway by the P2Y(12) receptor reverses differentiation into enhanced proliferation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-methylthio-ADP,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Monophosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Fibrillary Acidic Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/P2ry12 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/P2y12 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Purinergic P2 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Purinergic P2 Receptor Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2Y12,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/cangrelor
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
89
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
442-53
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15056287-Adenosine Diphosphate,
pubmed-meshheading:15056287-Adenosine Monophosphate,
pubmed-meshheading:15056287-Adenylate Cyclase,
pubmed-meshheading:15056287-Adrenergic beta-Agonists,
pubmed-meshheading:15056287-Animals,
pubmed-meshheading:15056287-Cell Differentiation,
pubmed-meshheading:15056287-Cell Division,
pubmed-meshheading:15056287-Cell Line, Tumor,
pubmed-meshheading:15056287-Cyclic AMP,
pubmed-meshheading:15056287-Enzyme Inhibitors,
pubmed-meshheading:15056287-GTP-Binding Protein alpha Subunits, Gi-Go,
pubmed-meshheading:15056287-Glial Fibrillary Acidic Protein,
pubmed-meshheading:15056287-Glioma,
pubmed-meshheading:15056287-Membrane Proteins,
pubmed-meshheading:15056287-Pertussis Toxin,
pubmed-meshheading:15056287-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15056287-Phosphorylation,
pubmed-meshheading:15056287-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15056287-Proto-Oncogene Proteins,
pubmed-meshheading:15056287-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15056287-Purinergic P2 Receptor Agonists,
pubmed-meshheading:15056287-Purinergic P2 Receptor Antagonists,
pubmed-meshheading:15056287-Rats,
pubmed-meshheading:15056287-Receptors, Adrenergic, beta,
pubmed-meshheading:15056287-Receptors, Purinergic P2,
pubmed-meshheading:15056287-Receptors, Purinergic P2Y12,
pubmed-meshheading:15056287-Thionucleotides
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pubmed:year |
2004
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pubmed:articleTitle |
P2Y12 receptor stimulation inhibits beta-adrenergic receptor-induced differentiation by reversing the cyclic AMP-dependent inhibition of protein kinase B.
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pubmed:affiliation |
Laboratory of Cellular Biochemistry, Department of Biomedical Sciences, University of Antwerp, Wilrijk-Antwerpen, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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