The glucagon superfamily: precursor structure and gene organization.

The glucagon superfamily includes the polypeptides glucagon, secretin, vasoactive inhibitory peptide (VIP), gastric inhibitory peptide and growth hormone-releasing factor (GHRF). Complementary DNA clones which encode the precursors to glucagon, VIP and GHRF have been isolated. Although the sizes and sequences of preproglucagon, prepro VIP and preproGHRF are distinct, the structural organization of the three precursors is similar. Each has a signal peptide, an NH2-terminal peptide and one, two or three peptides whose sequences are related to glucagon. Prepro VIP and preproGHRF also have a COOH-terminal peptide. The sequences of two different anglerfish preproglucagon molecules have been determined and they contain the sequences of glucagon and a related peptide. In contrast, hamster, cow and rat preproglucagon contain the sequences of glucagon and two related peptides. Human and rat prepro VIP contain the sequences of VIP and the related peptide PHM/PHI-27. Human and rat preproGHRF contain the sequence of only one peptide related to glucagon, i.e., GHRF. The genes for both preproglucagon and preproGHRF have been isolated. Their exon-intron organization indicates that each exon encodes a functionally distinct region of the precursor and mRNA.