Figure 1
From: Molecular mechanisms mediating the G protein-coupled receptor regulation of cell cycle progression
Modulation of intracellular cAMP levels by GPCR-coupled mechanisms affects cell cycle progression. Agonist activation of Gs-coupled receptors promotes increased AC activity and cAMP accumulation. Subsequent PKA activation leads to the activation of the transcription factor CREB and the regulation of the expression of cyclins and the CDK inhibitor p27Kip1. The resulting effect on cell cycle progression is dependent on a number of factors, including the concentration of cAMP generated. PKA can also regulate, positively or negatively, other mitogenic pathways, particularly those leading to the activation of MAPKs, (see text for further details). Activation of the AC/cAMP/PKA axis can be antagonized by the activation of GPCRs coupled to Gi/o-family proteins. However, the definitive involvement of these MAPK and Gi/o-coupled pathways in regulating proliferation has not been established (indicated by dashed lines).