Inhibition of proto-oncogene c-fos transcription by inhibitors of protein kinase C and ion transport.
Both 4 beta-phorbol 12,13-didecanoate (PDD) and calcium ionophore A23187 induced c-fos mRNA accumulation with similar kinetics in human monocyte-like cells (U937). Their effects were additive. Cells pretreated with PDD were not induced to accumulate c-fos mRNA by PDD but remained responsive to the induction by A23187. Similarly cells pretreated with A23187 responded to PDD but not to A23187. Nuclear run-off transcription assay indicated that increase in the c-fos mRNA level after the second inducer treatment corresponded to transcriptional activation of the c-fos gene. The accumulation of c-fos mRNA and the transcriptional activation of c-fos induced by PDD or A23187 were inhibited by the protein kinase inhibitor H-7 and by quinidine and amiloride. The induction by A23187, but not that by PDD, was also inhibited by 4-aminopyridine, or tetraethylammonium. From these results, it is proposed that activation of protein kinase C and Na+ or K+ transport are required for c-fos induction caused by PDD and A23187.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015761:4-Aminopyridine; D000584:Amiloride / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D011802:Quinidine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
D000631:Aminopyridines; D007546:Isoquinolines; C000715470:MAS1 protein, human; D010703:Phorbol Esters; D010879:Piperazines; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D013757:Tetraethylammonium Compounds; C008876:phorbol-12,13-didecanoate; D000001:Calcimycin; D000584:Amiloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D015761:4-Aminopyridine; D011493:Protein Kinase C; D011802:Quinidine; D011188:Potassium