EFFECTS OF cAMP ON ERK MITOGEN-ACTIVATED PROTEIN KINASE ACTIVITY IN HEPATOCYTES DO NOT PARALLEL THE BIDIRECTIONAL REGULATION OF DNA SYNTHESIS
✍ Scribed by G.Hege Thoresen; Ellen Joanne Johasen; Thoralf Christoffersen
- Publisher
- Elsevier Science
- Year
- 1999
- Tongue
- English
- Weight
- 252 KB
- Volume
- 23
- Category
- Article
- ISSN
- 1065-6995
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✦ Synopsis
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 24h, 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.