Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription

Science. 1990 Aug 3;249(4968):533-7. doi: 10.1126/science.2166335.

Abstract

Phosphoenolpyruvate carboxykinase (PEPCK) governs the rate-limiting step in gluconeogenesis. Glucocorticoids and adenosine 3',5'-monophosphate (cAMP) increase PEPCK gene transcription and gluconeogenesis, whereas insulin has the opposite effect. Insulin is dominant, since it prevents cAMP and glucocorticoid-stimulated transcription. Glucocorticoid and cAMP response elements have been located in the PEPCK gene and now a 15-base pair insulin-responsive sequence (IRS) is described. Evidence for a binding activity that recognizes this sequence is presented.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / physiology
  • Dexamethasone / pharmacology
  • Genes, Regulator*
  • Insulin / pharmacology*
  • Molecular Sequence Data
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics*
  • Phosphoenolpyruvate Carboxykinase (GTP) / metabolism
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / metabolism
  • Thionucleotides
  • Transcription, Genetic / drug effects*
  • Transfection

Substances

  • Insulin
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Thionucleotides
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
  • Dexamethasone
  • Cyclic AMP
  • Chloramphenicol O-Acetyltransferase
  • Phosphoenolpyruvate Carboxykinase (GTP)