Isolation of a cDNA clone encoding pancreatic polypeptide.

We have isolated a cDNA clone encoding pancreatic polypeptide from a cDNA library constructed with RNA from an endocrine neoplasm of the human pancreas. The cDNA was inserted into plasmid pBR322 and the plasmid was cloned in Escherichia coli. Oligonucleotides (sequence in text) specific for the amino acid sequence (sequence in text) of pancreatic polypeptide were used as hybridization probes. The pancreatic polypeptide cDNA isolated was 465 base pairs long and encoded a peptide of 95 amino acids in the coding region. The 36-amino acid sequence of pancreatic polypeptide was flanked by a 29-amino acid putative leader sequence at the amino terminus and a connecting tripeptide (Gly-Lys-Arg) followed by a 27-amino acid peptide at the carboxyl terminus. The first 20 of the amino acids in the carboxyl-terminal heptacosapeptide were identical to the structure of human pancreatic icosapeptide with the single exception of an isoleucine substitution for valine in the 18th position. This alteration results from an A----G substitution in the nucleotide sequence of the cDNA and may represent a genetic variation or a point mutation in the pancreatic polypeptide cDNA.