cAMP-dependent positive control of cyclin A2 expression during G1/S transition in primary hepatocytes

cAMP positively and negatively regulates hepatocyte proliferation but its m olecular targets are still unknown. Cyclin A2 is a major regulator of the c ell cycle progression and its synthesis is required for progression to S ph ase. We have investigated whether cyclin A2 and cyclin A2-associated kinase might be one of the targets for the cAMP transduction pathway during progr ession of hepatocytes through G1 and G1/S. We show that stimulation of prim ary cultured hepatocytes by glucagon differentially modulated the expressio n of G1/S cyclins. Glucagon indeed upregulated cyclin A2 and cyclin A2-asso ciated kinase while cyclin E-associated kinase was unmodified. In conclusio n, our study identifies cyclin A2 as an important effector of the cAMP tran sduction network during hepatocyte proliferation. (C) 1999 Academic Press.