6 - The mosaic evolution of the pancreatic polypeptide gene

Summary

Introduction

Pancreatic polypeptide, a 36 amino acid carboxyamidated peptide hormone, is synthesized in the PP cells of the islets of Langerhans (Solcia et al, 1985). The polypeptide has been reported to modulate insulin and somatostatin secretion (Murphy et al, 1981; Trimble et al, 1982) and to inhibit pancreatic exocrine and gastric secretion (Adrian et al, 1981; Hazelwood, 1981). In canine islet cells, the pancreatic polypeptide precursor was demonstrated to be posttranslationally processed to produce pancreatic polypeptide and an icosapeptide, a second stable product derived from the carboxy-terminal region of the precursor (Schwartz & Tager, 1981). Icosapeptide-like peptides have also been detected in human, sheep and cat pancreases (Schwartz et al, 1984; Nielsen et al, 1986). However, in 1986 Yamamoto et al. demonstrated that rat pancreatic polypeptide precursor deduced from the nucleotide sequence of the pancreatic polypeptide precursor mRNA did not contain any sequence similar to the icosapeptide (Yamamoto et al, 1986). Recent characterizations of several mammalian pancreatic polypeptide mRNAs (Boel et al., 1984; Toothman & Paquette, 1987; Yonekura et al, 1988; Blackstone et al, 1988) have shown that the pancreatic polypeptide domain of the precursor is well conserved, whereas there is a high degree of divergence in the carboxy-terminal domain; the mouse and guinea pig precursors also contained no sequence similar to the icosapeptide.