Regulation of AP-1 activity in glucose-stimulated insulinoma cells.
The transcriptional activity of AP-1 has been analyzed in glucose-stimulated INS-1 insulinoma cells using a chromosomally embedded AP-1-responsive reporter gene. We show that AP-1 activity was significantly elevated in glucose-treated INS-1 cells. Preincubation of the cells with nifedipine or expression of the Ca(2+) binding protein parvalbumin in the cytoplasm of INS-1 cells reduced AP-1 activity. Thus, activation of L-type Ca(2+) channels and an elevated cytoplasmic Ca(2+) concentration are crucial to connecting glucose stimulation with enhanced AP-1 activity. Expression of dominant negative forms of A-Raf, MKK4 or MKK6 and pharmacological inhibition of MEK and p38 revealed that extracellular signal-regulated protein kinase, p38 and c-Jun NH(2)-terminal protein kinase participate in the upregulation of AP-1 activity. Expression of dominant-negative mutants of c-Jun and Elk-1 reduced AP-1 transcriptional activity in INS-1 cells indicating that c-Jun and ternary complex factors are involved in the regulation of AP-1 activity in glucose-stimulated insulinoma cells.
Müller
Isabelle
I
Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, D-66421 Homburg, Germany.
Endo
Takeshi
T
Thiel
Gerald
G
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009543:Nifedipine / Q000494:pharmacology; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010320:Parvalbumins; D018808:Transcription Factor AP-1; D050807:ets-Domain Protein Elk-1; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D009543:Nifedipine; D005947:Glucose; D002118:Calcium