cAMP-dependent positive control of cyclin A2 expression during G1/S transition in primary hepatocytes.
cAMP positively and negatively regulates hepatocyte proliferation but its molecular targets are still unknown. Cyclin A2 is a major regulator of the cell cycle progression and its synthesis is required for progression to S phase. We have investigated whether cyclin A2 and cyclin A2-associated kinase might be one of the targets for the cAMP transduction pathway during progression of hepatocytes through G1 and G1/S. We show that stimulation of primary cultured hepatocytes by glucagon differentially modulated the expression of G1/S cyclins. Glucagon indeed upregulated cyclin A2 and cyclin A2-associated kinase while cyclin E-associated kinase was unmodified. In conclusion, our study identifies cyclin A2 as an important effector of the cAMP transduction network during hepatocyte proliferation.
INSERM U370, Faculté Necker, 156 rue de Vaugirard, Paris Cédex 15, 75730, France.
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C
Desdouets
G H
GH
Thoresen
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Senamaud-Beaufort
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T
Christoffersen
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Brechot
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J
Sobczak-Thepot
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism*; D056751:Cyclin A2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D016193:G1 Phase / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
C503722:Ccna2 protein, rat; D019925:Cyclin A; D056751:Cyclin A2; D016213:Cyclins; D004247:DNA; D005934:Glucagon; D000242:Cyclic AMP; D018844:Cyclin-Dependent Kinases