RAS ANTAGONIZES CAMP-STIMULATED GLUCAGON GENE-TRANSCRIPTION IN PANCREATIC-ISLET CELL-LINES

Ras, a GTP-binding protein, converts membrane tyrosine kinase signalli ng to changes in gene expression patterns. Utilising a rat glucagon pr omoter-CAT construct (p[-1.1]GLU-CAT) we demonstrate in transient tran sfection experiments that the oncogenic Ras inhibits cAMP-dependent ac tivation of p[-1.1]GLU-CAT in both glucagonoma InR 1-G9 and insulinoma beta-TCl cells. Conversely, the expression of a dominant negative mut ant of Ras enhances the cAMP-induced activation of p[-1.1]GLU-CAT tran scription in these cells. Our data suggests a functional interference of Ras with the cAMP-dependent transcription of the glucagon gene.