Glucose stimulates the activation domain potential of the PDX-1 homeodomain transcription factor.
Glucose-stimulated expression of the insulin gene in beta cells is mediated by the PDX-1 transcription factor. In this report, we show that stimulation results from effects on activation and DNA-binding potential. Thus, glucose specifically stimulated expression in MIN6 beta cells from chimeras of PDX-1 and the GAL4 DNA-binding domain which spanned the N-terminal PDX-1 activation domain located between amino acids 1 to 79. GAL4:PDX activity was induced over physiological glucose concentrations and was also regulated by effectors of this response. The level of endogenous PDX-1 binding and phosphorylation were also induced under these conditions. We discuss how changes in PDX-1 phosphorylation may influence activity in glucose-treated beta cells.
Hagedorn Research Laboratory, Gentofte, Denmark.
H V
HV
Petersen
M
M
Peshavaria
A A
AA
Pedersen
J
J
Philippe
R
R
Stein
O D
OD
Madsen
P
P
Serup
D001483:Base Sequence; D002460:Cell Line; D015342:DNA Probes; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation
D015342:DNA Probes; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D018398:Homeodomain Proteins; D007328:Insulin; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose