Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription.
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.
O'Brien
R M
RM
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0615.
Lucas
P C
PC
Forest
C D
CD
Magnuson
M A
MA
Granner
D K
DK
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D005809:Genes, Regulator; D007328:Insulin / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013873:Thionucleotides; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D007328:Insulin; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D003907:Dexamethasone; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)