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Ras antagonizes cAMP stimulated glucagon gene transcription in pancreatic islet cell lines
R Gherzi1, P Briata, H C Fehmann
1Department of Internal Medicine, Philipps University, Marburg, Germany.
FEBS Letters
|October 24, 1994
Abstract:
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.