title: Stimulation of prohormone convertase-1 mRNA expression by second messenger signaling systems.
abstract: The purpose of this study was to investigate the effects of activation of various second messenger signaling systems on gene expression (i.e. mRNA levels) of a peptide hormone processing enzyme called prohormone convertase-1 (PC-1, also called PC-3) in a human pancreatic carcinoid cell line (BON) that expresses several endocrine peptides (chromogranin A, pancreastatin, neurotensin). Pharmacologic activation of adenylate cyclase-cAMP, protein kinase-C and Ca2+ mobilization pathways increased PC-1 mRNA levels and neurotensin secretion. Elevations in PC-1 mRNA levels were dose and time-related. Secretagogue-induced cellular depletion of neurotensin was followed by a replenishment of cellular neurotensin stores and an upregulation of PC-1 mRNA levels. Together, these data indicate that PC-1 mRNA expression is increased with peptide secretion and coordinated with maintenance of cellular stores of peptides.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston 77555, USA.
authors.forename: V
authors.initials: V
authors.lastname: Udupi
authors.forename: C M
authors.initials: CM
authors.lastname: Townsend
authors.forename: G H
authors.initials: GH
authors.lastname: Greeley
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology; D009496:Neurotensin / Q000378:metabolism; D043484:Proprotein Convertases; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D015290:Second Messenger Systems; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D007476:Ionophores; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D009496:Neurotensin; D000242:Cyclic AMP; D011493:Protein Kinase C; D043484:Proprotein Convertases; D016282:Aspartic Acid Endopeptidases; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium