The signalling pathways of G-protein coupled receptors (GPCRs) and epidermal growth factor receptors (EGFRs) have been shown to communicate in mitogenic processes in many cells. Several mechanisms have been suggested to explain this; in particular transactivation is a mechanism that seems to be involved in many cases where signalling pathways intermingle. We have observed that prostaglandin E2 (PGE2) and other GPCR ligands enhance the mitogenic effect of epidermal growth factor (EGF) on hepatocytes. In this study we suggest that cross-talk between the pathways activated by these two agonists is not dependent on transactivation but a result of altered gene transcription caused by stimulation with PGE2. Our results indicate that transcription is altered so as to induce proteins that prolongate signalling in the EGFR pathway. These proteins inhibit the deactivation of the extracellular-regulated kinase (ERK), which is an important component in the pathway dowstream of the EGFR.