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

V. C. Schadlow, N. Barzilai, P. J. Deutsch

Research output: Contribution to journalArticle

35 Scopus citations

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
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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