EGF and TPA stimulate de novo synthesis of PGHS-1 and PGHS-2 through different signal transduction pathways.
Epidermal growth factor (EGF) as well as phorbol 12-myristate 13-acetate (TPA) stimulate de novo synthesis of PGHS (prostaglandin H synthase)-1 and PGHS-2 mRNA, resulting in increased production of PGE2 in rat tracheal epithelial cells (RTE, EGV-6 cells). Stimulation of PGE2 production by TPA is more potent than that by EGF. Staurosporine and H-7, protein kinase C (PKC) inhibitors, suppressed the increase of mRNA and PGE2 levels caused by TPA, but not that caused by EGF. On the other hand, methyl 2,5-dihydroxycinnamate, a tyrosine kinase inhibitor (TKI), suppressed the increase of mRNA and PGE2 levels caused by EGF, but not that caused by TPA. These results indicate that EGF stimulates de novo synthesis of PGHS-1 and PGHS-2 mRNA through a signal transduction pathway which is independent from PKC-associated mechanisms but dependent upon the tyrosine kinase activity of the EGF receptor.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002461:Cell Line, Transformed; D002934:Cinnamates / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014132:Trachea / Q000378:metabolism
D000470:Alkaloids; D002934:Cinnamates; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; C067472:methyl 2,5-dihydroxycinnamate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate