Ras antagonizes cAMP stimulated glucagon gene transcription in pancreatic islet cell lines.
Ras, a GTP-binding protein, converts membrane tyrosine kinase signalling to changes in gene expression patterns. Utilising a rat glucagon promoter-CAT construct (p[-1.1]GLU-CAT) we demonstrate in transient transfection experiments that the oncogenic Ras inhibits cAMP-dependent activation of p[-1.1]GLU-CAT in both glucagonoma InR1-G9 and insulinoma beta-TC1 cells. Conversely, the expression of a dominant negative mutant of Ras enhances the cAMP-induced activation of p[-1.1]GLU-CAT transcription in these cells. Our data suggests a functional interference of Ras with the cAMP-dependent transcription of the glucagon gene.
Department of Internal Medicine, Philipps University, Marburg, Germany.
R
R
Gherzi
P
P
Briata
H C
HC
Fehmann
B
B
Göke
D007516:Adenoma, Islet Cell; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005799:Genes, Dominant / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D005934:Glucagon / Q000235:genetics*; D005935:Glucagonoma / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism*; D009154:Mutation / Q000502:physiology; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D005934:Glucagon; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D018631:ras Proteins