PACAP stimulates transcription of c-Fos and c-Jun and activates the AP-1 transcription factor in rat pancreatic carcinoma cells.
Pituitary Adenylate Cyclase Activating Peptide (PACAP) strongly induces proliferation of the rat pancreatic carcinoma cell line AR4-2J via interaction with the G-protein coupled type 1 PACAP/VIP (PVI) receptor. RT-PCR analysis revealed that this mitogenic effect of PACAP is preceded by a rapid and transient increase of transcription of the protooncogene c-fos and to a lesser extent of c-jun. Transcriptional activation is abolished by a specific PACAP antagonist and by inhibitors of PKC and PKA. In parallel to c-fos/c-jun induction, PACAP rapidly activates the heterodimeric transcription factor AP-1, as shown by electrophoretic mobility shift assay. These findings demonstrate that signal transduction of a growth-stimulating G-protein-coupled receptor involves the c-fos/c-jun/AP-1 cascade, a pathway mainly linked to classical growth factor receptor tyrosine kinases.
Schäfer
H
H
Laboratory of Molecular Gastroenterology, Gastrointestinal Unit, First Department of Medicine, Christian-Albrechts-University, Kiel, Germany.
Zheng
J
J
Gundlach
F
F
Günther
R
R
Schmidt
W E
WE
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D051381:Rats; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
C495403:Adcyap1 protein, rat; D017931:DNA Primers; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1