Regulation of gene expression in PC12 cells via an activator of dual second messengers: Pituitary adenylate cyclase activating polypeptide

Valerie C. Schadlow, Nir Barzilai, Paul J. Deutsch

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

In this study we demonstrate that the activator protein-1 (AP-1) DNA motif, initially considered to be unresponsive to cyclic AMP (cAMP), does function as a cAMP-response element in PC12 cells. A luciferase reporter gene driven by the collagenase promoter that contains the AP-1 motif is responsive to cAMP as well as phorbol esters when transfected in PC12 cells. We have recently shown that pituitary adenylate cyclase activating peptide (PACAP) has neurotrophic properties and activates both adenylylcyclase and the inositol lipid cascade in PC12 cells. Consistent with these actions, we demonstrate that PACAP is an effective activator of luciferase reporter genes whose promoters bear the AP-1 motif, as well as the related DNA element that binds the protein CREB. Both the cAMP and inositol lipid pathways appear to play a role in the activation of these motifs by PACAP. Mutation of the AP-1 motif and its juxtaposition to a heterologous promoter proves that the AP-1 motif is a locus for response to cAMP and PACAP. The luciferase reporter genes bearing the AP-1 motif are not cAMP responsive in HeLa tk- cells, indicating that the mode of second-messenger responsiveness is cell-type specific.

Original languageEnglish (US)
Pages (from-to)941-951
Number of pages11
JournalMolecular Biology of the Cell
Volume3
Issue number8
StatePublished - 1992

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Pituitary Adenylate Cyclase-Activating Polypeptide
PC12 Cells
Transcription Factor AP-1
Gene Expression Regulation
Second Messenger Systems
Amino Acid Motifs
Cyclic AMP
Adenylyl Cyclases
Luciferases
Reporter Genes
Peptides
Inositol
Lipids
Cyclic AMP Response Element-Binding Protein
Nucleotide Motifs
Response Elements
Phorbol Esters
Collagenases
HeLa Cells
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Regulation of gene expression in PC12 cells via an activator of dual second messengers : Pituitary adenylate cyclase activating polypeptide. / Schadlow, Valerie C.; Barzilai, Nir; Deutsch, Paul J.

In: Molecular Biology of the Cell, Vol. 3, No. 8, 1992, p. 941-951.

Research output: Contribution to journalArticle

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