Transforming growth factor beta increases the activity of phosphatidate phosphohydrolase-1 in rat hepatocytes

Phosphatidic acid (PA) is a potent second messenger arising from growth factor-induced stimulation of phospholipase D which hydrolyses phosphatidylcholine. PA is hydrolysed to diacylglycerol by PA phosphohydrolase (PAP) which exists in two forms: PAP-1 and PAP-2. In rat hepatocyte cultures, overnight (20h) incubation with transforming growth factor (TGF) beta (1 ng/ml) increased PAP-1 activity two-fold. This effect was concentration and time dependent and was greatest at low cell density. The TGFbeta effect on PAP-1 was additive to stimulation induced by dexamethasone but not by glucagon and it reversed the inhibition by insulin. Epidermal growth factor had no effect on PAP-1 activity. None of the above hormones or growth factors affected the subcellular distribution of PAP-1. Stimulation of PAP-1 by TGFbeta may be involved in mediating some of its biological effects.