title: Regulatory mechanism of PAC1 gene expression via Sp1 by nerve growth factor in PC12 cells.
abstract: In addition to VPAC1 and VPAC2, PAC1 is involved in the pleiotropic action of pituitary adenylate cyclase activating polypeptide (PACAP) in the CNS. A luciferase reporter assay for the human PAC1 gene (-2160/+268) revealed that NGF treatment significantly augments the promoter activity of the PAC1 gene. Moreover, the Sp1 site at -282/-273 was shown to be essential for the NGF-augmented promoter activity of the PAC1 gene. Treatment with U0126, an MEK inhibitor, or Mithramycin A, an Sp1 inhibitor, significantly attenuated promoter activity. These results indicate that activation of Sp1 by the Ras/MAPK pathway might participate in neuron specific expression of the PAC1 gene.
authors.affiliation: Department of Pharmacology, Graduate School of Medical and Dental Sciences, University of Kagoshima, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Miura
authors.forename: Naoko
authors.initials: N
authors.lastname: Odahara
authors.forename: Aiko
authors.initials: A
authors.lastname: Tominaga
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Inoue
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kambe
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurihara
authors.forename: Atsuro
authors.initials: A
authors.lastname: Miyata
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009414:Nerve Growth Factors / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D009841:Oligonucleotides / Q000494:pharmacology; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002070:Butadienes; D009414:Nerve Growth Factors; D009570:Nitriles; D009841:Oligonucleotides; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D016329:Sp1 Transcription Factor; C113580:U 0126; D049410:Luciferases, Renilla; D020930:MAP Kinase Kinase Kinases