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.
MeSH terms
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Adenoma, Islet Cell
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Animals
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Cyclic AMP / physiology
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Cyclic AMP-Dependent Protein Kinases / physiology
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Genes, Dominant / genetics
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Genes, ras / genetics
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Glucagon / genetics*
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Glucagonoma / metabolism*
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Insulinoma / metabolism*
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Mutation / physiology
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Promoter Regions, Genetic
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Protein Kinase C / physiology
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RNA, Messenger / biosynthesis
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Rats
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Recombinant Fusion Proteins / biosynthesis
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Signal Transduction / physiology
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Transcription, Genetic / physiology*
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Transfection
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Tumor Cells, Cultured
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ras Proteins / genetics
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ras Proteins / physiology*
Substances
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RNA, Messenger
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Recombinant Fusion Proteins
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Glucagon
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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ras Proteins