Cyclic AMP Stimulates Somatostatin Gene Transcription by Phosphorylation of CREB at Serine 133

Cell. 1989 Nov 17;59(4):675-80. doi: 10.1016/0092-8674(89)90013-5.

Abstract

In this paper, we demonstrate that phosphorylation of CREB at Ser-133 is induced 6-fold in vivo, following treatment of PC12 cells with forskolin. By contrast, no such induction was observed in the kinase A-deficient PC12 line A126-1B2 (A126). Using F9 teratocarcinoma cells, which are unresponsive to cAMP, we initiated a series of transient expression experiments to establish a causal link between phosphorylation of CREB and trans-activation of cAMP-responsive genes. Inactivating the kinase A phosphorylation site by in vitro mutagenesis of the cloned CREB cDNA at Ser-133 completely abolished CREB transcriptional activity. As CREB mutants containing acidic residues in place of the Ser-133 phosphoacceptor were also transcriptionally inactive, these results suggest that phosphorylation of CREB may stimulate transcription by a mechanism other than by simply providing negative charge.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Gland Neoplasms
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Colforsin / pharmacology*
  • Cyclic AMP / physiology*
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / metabolism*
  • Genes / drug effects*
  • Molecular Sequence Data
  • Mutation
  • Peptide Mapping
  • Pheochromocytoma
  • Phosphorylation
  • Rats
  • Serine*
  • Somatostatin / genetics*
  • Transcription, Genetic / drug effects*
  • Transfection

Substances

  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Colforsin
  • Serine
  • Somatostatin
  • Cyclic AMP