Staurosporine potentiates cAMP-mediated promoter activity of the vasoactive intestinal polypeptide gene in rat pheochromocytoma PC12 cells.
The potent protein kinase inhibitor staurosporine enhances cAMP-mediated responses in human neuroblastoma cells as represented by neurite extension and induction of tyrosine hydroxylase. To explore how staurosporine regulates cAMP signaling pathway, we examined transcriptional activity of the human vasoactive intestinal polypeptide (VIP) gene promoter carrying a cAMP-responsive element. In PC12 cells stably transfected with a reporter plasmid, staurosporine alone had little effect; however, in combination with forskolin or dibutyryl cAMP, staurosporine dose-dependently (1-50 nM) enhanced cAMP-mediated transcription from the VIP gene promoter, which was comparable to that maximally induced by cAMP plus 12-O-tetradecanoylphorbol-13-acetate. This is the first report of potentiation of cAMP-mediated promoter activity by staurosporine in neuroendocrine cells.
Sasaki
K
K
Growth Factor Division, National Cancer Center Research Institute, Tokyo, Japan.
Tsukada
T
T
Adachi
I
I
Yamaguchi
K
K
D000310:Adrenal Gland Neoplasms; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009447:Neuroblastoma; D016716:PC12 Cells; D010673:Pheochromocytoma; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D019311:Staurosporine; D014162:Transfection; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis* / Q000235:genetics*; D001616:beta-Galactosidase / Q000096:biosynthesis
D000470:Alkaloids; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; D001616:beta-Galactosidase; D019311:Staurosporine