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.
Desdouets
C
C
INSERM U370, Faculté Necker, 156 rue de Vaugirard, Paris Cédex 15, 75730, France.
Thoresen
G H
GH
Senamaud-Beaufort
C
C
Christoffersen
T
T
Brechot
C
C
Sobczak-Thepot
J
J
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