cDNA cloning of proglucagon from the stomach and pancreas of the dog.
In human and rat, tissue-specific proteolytic processing of identical proglucagon precursors yield tissue-specific proglucagon-derived peptides. In contrast, in many non-mammalian vertebrates alternative mRNA splicing yields different proglucagon precursors in different tissues. Thus alternative mRNA splicing, in part, limits the choices of proglucagon-derived peptides that can be produced by proteolytic processing. Stomach proglucagon mRNAs from the rainbow trout and Xenopus laevis were found not to encode the proglucagon-derived peptide glucagon-like peptide 2 (GLP-2). To determine if the absence of GLP-2 was a general feature of stomach proglucagons we isolated and characterized proglucagon cDNAs from the stomach and the pancreas of the dog, a mammal that expresses the proglucagon gene in the stomach. A major proglucagon transcript of about 1100 bases and a minor transcript of about 800 bases were identified in both stomach and pancreas. The coding sequences of both the stomach and pancreatic proglucagon transcripts were identical. Therefore, tissue-specific proteolytic processing, and not alternative mRNA splicing, must regulate the production of tissue-specific proglucagon-derived peptides from the stomach of the dog.
Irwin
D M
DM
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, Banting and Best Diabetes Centre, University of Toronto, Ont., Canada. david.irwin@utoronto.ca
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D005753:Gastric Mucosa / Q000378:metabolism*; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010179:Pancreas / Q000378:metabolism*; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA
D018076:DNA, Complementary; D011498:Protein Precursors; D052336:Proglucagon; D005934:Glucagon