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 β-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.