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.
Dixon
M C
MC
Department of Medicine, Medical School, University of Newcastle, Framlington Place, Newcastle upon Tyne, United Kingdom.
Yeaman
S J
SJ
Agius
L
L
Day
C P
CP
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D000073718:Pancreatitis-Associated Proteins; D010711:Phosphatidate Phosphatase / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007328:Insulin; D007527:Isoenzymes; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D005934:Glucagon; D010711:Phosphatidate Phosphatase