Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem.

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Abstract
Recombinant plasmids were constructed containing DNA complementary [c] to the mRNA encoding a pancreatic preproglucagon (MW 14,500), a product of cell-free translation of angler fish islet mRNA shown previously by immunoprecipitation analyses to be a precursor of glucagon. cDNA of 630, 180 and 120 base pairs were isolated and correspond to most of the mRNA for the preproglucagon (650 bases). The cDNA contain a protein coding sequence of 372 nucleotides and 5''- and 3''-untranslated regions of 58 and 206 nucleotides, respectively. From the coding sequence of the cDNA, the sequence of glucagon, identical to mammalian glucagon in 20 of 29 positions, was found to reside in the preproglucagon of 124 amino acids flanked by NH2- and COOH-peptide extensions of 52 and 43 amino acids, respectively. The peptide extensions are linked to the glucagon by Lys-Arg sequences characteristic of the sites that are cleaved during the posttranslational processing of prohormones. Notable is the finding that, following the initial Lys-Arg sequence in the COOH-peptide extension is a pentapeptide, Ser-Gly-Val-Ala-Glu, followed by another Lys-Arg and a sequence of 34 residues that shows striking homology with glucagon and the other peptides of the glucagon family.sbd.gastric inhibitory peptide, vasoactive intestinal peptide and secretin. Thus, the preproglucagon mRNA contains 2 glucagon-related coding sequences arranged in tandem. The finding of Lys-Arg sequences flanking the glucagon and glucagon-related sequences suggests that these 2 peptides and a pentapeptide are formed in vivo by posttranslational cleavages of a common precursor.