Calcium induction of the mRNAs for prolactin and c-fos is independent of protein kinase C activity.
Ca2+ is a strong regulator of the expression of a limited number of eukaryotic genes, including prolactin and c-fos. However, little is known about the cellular signal transduction pathways involved in the action of this ion on specific gene expression. The Ca2+-dependent enzyme protein kinase C has been implicated in other transcriptional pathways regulating the prolactin and c-fos genes. We therefore employed down-regulation of protein kinase C in rat pituitary cells to investigate whether this enzyme is involved in Ca2+ regulation of expression of either of these genes. Exposure of Ca2+-deprived GH3 cells to this ion in the presence of the Ca2+ channel modulator Bay K8644 yielded large increases in the mRNAs for both prolactin and c-fos. Incubation of cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) yielded a 7- to 15-fold decrease in the enzymatic activity of C kinase assayed in vitro, but little or no effect on Ca2+ stimulation of cellular levels of either mRNA. The latter observation was apparently not due simply to an inability of TPA to down-regulate the gene-regulatory activity of kinase C in intact GH3 cells, since this phorbol ester blocked the stimulation by platelet-derived growth factor of cellular levels of c-fos mRNA. TPA treatment also yielded no significant effect on the kinetics of the Ca2+-stimulated accumulation of either mRNA, implying that kinase C is not required at any stage of the Ca2+ induction of these two genes.
Bandyopadhyay
S K
SK
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York 10029.
Bancroft
C
C
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D010902:Pituitary Gland / Q000201:enzymology / Q000378:metabolism; D011388:Prolactin / Q000096:biosynthesis / Q000235:genetics*; D011493:Protein Kinase C / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011388:Prolactin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium