β-Adrenergic stimulation of cFOS via protein kinase A is mediated by cAMP regulatory element binding protein (CREB)-dependent and tissue-specific CREB- independent mechanisms in corticotrope cells

A. L. Boutillier, F. Barthel, J. L. Roberts, J. P. Loeffler

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Catecholamines stimulate proopiomelanocortin (POMC) gene expression in corticotrope cells, but the molecular mechanisms of these effects are not known. While β-adrenergic receptors stimulate the protein kinase A (PKA) system, the POMC promoter does not have classical cAMP-response elements (CREs). Therefore, we investigated the induction of the c-fos protooncogene, previously shown to increase POMC transcription in AtT20 cells. In this corticotrope-derived cell line, we show that activation of β-receptors with isoprenalin (Iso) induces a transient rise in c-fos mRNA levels. Gel mobility shift assays with a labeled AP1 consensus sequence (TGACTCA) showed induction of specific binding activity after Iso treatment. Cotransfection experiments with dominant inhibitory PKA mutants and reporter genes containing c-fos promoter sequences showed that c-fos induction by Iso is entirely dependent on a functional PKA activity. Furthermore, we show that β-receptor induction of c-fos in corticotrophs is mediated by at least two distinct cAMP- responsive sequences. cAMP regulatory element binding (CREB)-dependent induction is observed on the CRE located at -60 bp on the c-fos promoter. A region located in the vicinity of the dyad symetry element (-290) is also found to mediate tissue-specific cAMP induction. Transcriptional activation by this site, although sensitive to PKA antagonism, is not blocked by CREB mutants.

Original languageEnglish (US)
Pages (from-to)23520-23526
Number of pages7
JournalJournal of Biological Chemistry
Volume267
Issue number33
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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