title: Activation of protein kinase C sensitizes the cyclic AMP signalling system of T51B rat liver cells.
abstract: Activation of protein kinase C (PKC) by phorbol esters (TPA) results in a modification of the cyclic AMP system leading to either attenuation or amplification of the cyclic AMP signal. In the non-neoplastic T51B rat liver cell line, TPA, when added to intact cells, had no effect on the basal level of cyclic AMP synthesis but caused a 1.5 fold amplification of the stimulation induced by beta-adrenergic agents, cholera toxin and forskolin. The effect appeared to be mediated by PKC since diacylglycerols caused the same amplification as did TPA while inactive phorbol esters were without effect. Phosphorylation of Gs or the catalytic subunit of adenylate cyclase by PKC is likely to be responsible for the enhancement of cyclic AMP synthesis. TPA also caused translocation of PKC; however, the time course of the translocation was longer than the time course of the enhancement of adenylate cyclase activity. Thus, the ability of TPA to amplify cyclic AMP synthesis is probably mediated by activation of PKC that is already present in the membrane.
authors.affiliation: Department of Pathology, Faculty of Health Sciences, University of Ottawa, Ontario, Canada.
authors.forename: L H
authors.initials: LH
authors.lastname: Aasheim
authors.forename: L P
authors.initials: LP
authors.lastname: Kleine
authors.forename: D J
authors.initials: DJ
authors.lastname: Franks
mesh_terms: D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology
chemical_list: D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate