Effects of cAMP on ERK mitogen-activated protein kinase activity in hepatocytes do not parallel the bidirectional regulation of DNA synthesis.
Previous studies have indicated that cAMP has bidirectional effects on epidermal growth factor (EGF)-induced DNA synthesis in cultured hepatocytes, acting to stimulate soon after plating (early G(1)) and to inhibit at later stages (nearer the G(1)/S transition). In this study we examined the role of the extracellular signal-regulated kinase (ERK) subgroup (p42/p44) of the mitogen activated protein (MAP) kinases both at growth-stimulatory and growth-inhibitory conditions. When added at low concentrations early during culturing, glucagon and 8-chlorophenylthio-cAMP (8-CPT-cAMP) did not increase MAP kinase activity, but enhanced the subsequent DNA synthesis. However, when administered at 24 h, glucagon and 8-CPT-cAMP decreased basal and EGF-induced MAP kinase activity and also inhibited EGF-induced DNA synthesis. Thus, although MAP kinase might play a role in the growth-inhibitory effect, it does not seem to be involved in growth-promoting regulation by cAMP in hepatocytes.
Thoresen
G H
GH
Department of Pharmacology, Faculty of Medicine, University of Oslo, Oslo, N-0316, Norway.
Johasen
E J
EJ
Christoffersen
T
T
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D004247:DNA; D000242:Cyclic AMP; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases