Down-regulation of the protein kinase A pathway by activators of protein kinase C and intracellular Ca2+ in fibroblast cells.
Many genes are regulated by the intracellular calcium, protein kinase C (PKC) and protein kinase A (PKA) pathways and it has been shown that these pathways synergize in some cell types, whereas they antagonize in others. Here we show that the calcium and PKC pathways suppress the effects mediated by the PKA pathway in a fibroblast cell line. The suppressing effect of elevated intracellular Ca2+ levels, but not of the PKC pathway, can be abrogated by the addition of cyclosporin A (CsA), indicating that the effect of Ca2+ is mediated by phosphatase-2B (PP-2B/calcineurin). Suppression by the PKC pathway is not mediated by the proto-oncogenes c-fos, c-jun and junB, as the co-transfection of these genes does not block the effects of the PKA stimulator 8-Br-cAMP. In addition, cotransfection with the catalytic subunit of PKA shows that the inhibitory effect of PKC occurs upstream of PKA activation.
Döbbeling
U
U
Institut für Veterinärbiochemie, Universität Zürich, Switzerland.
Berchtold
M W
MW
D016475:3T3 Cells; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis*; D016572:Cyclosporine / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D013729:Terpenes; D018808:Transcription Factor AP-1; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019284:Thapsigargin; D016572:Cyclosporine; D015500:Chloramphenicol O-Acetyltransferase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium