Anglerfish islet pre-proglucagon II: Nucleotide and corresponding amino acid sequence of the cDNA

Glucagon is a 29-amino acid peptide hormone that regulates blood glucose concentrations. It is a member of a family of structurally related hormones that includes in addition to glucagon, vasoactive intestinal peptide, gastric inhibitory peptide, and secretin. Like other peptide hormones, glucagon is synthesized as a larger precursor. Previously, we reported the amino acid sequence of an anglerfish pre-proglucagon of apparent M(r) = 14,500, derived from the sequence of cloned cDNAs. Now we have determined the nucleotide sequence of cDNAs encoding a separate anglerfish preproglucagon of apparent M(r) = 12,500 and have derived the complete amino acid sequence of this second precursor. The configurations of the two pre-proglucagons are similar. Each pre-proglucagon is a polyprotein that contains two glucagon-related peptides arranged in tandem, a 29-amino acid glucagon sequence and a 34-amino acid sequence which shows homology to glucagon and the other members of the glucagon family. These two peptides are linked in the precursors by lysine-arginine and intervening penta- or tetrapeptides. The glucagon sequences of 29 amino acids in the two precursors are closely homologous. Similarly, the 34-amino acid peptide sequences in the two precursors are highly homologous. Analyses of the genomic DNA prepared from the spleen of a single anglerfish show that these two pre-proglucagons are encoded by at least two separate genes. Analyses of the mRNAs in the anglerfish islets indicate that a single mRNA species encodes a M(r) = 14,500 pre-proglucagon but suggest that two separate mRNAs contain coding sequences for the M(r) = 12,500 pre-proglucagon. These studies indicate that in the anglerfish, glucagon is synthesized by way of the expression of at least two genes.