Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1984 Apr;3(4):909–912. doi: 10.1002/j.1460-2075.1984.tb01904.x

A cDNA encoding a small common precursor for human pancreatic polypeptide and pancreatic icosapeptide.

E Boel, T W Schwartz, K E Norris, N P Fiil
PMCID: PMC557446  PMID: 6373251

Abstract

A cDNA for the hormone, human pancreatic polypeptide (PP), was isolated by oligodeoxynucleotide screening from a cDNA library constructed from normal human pancreatic mRNA. The primary structure of the precursor protein as deduced from the cDNA sequence is 95 amino acids long and is composed of a typical, but rather long signal peptide of 29 residues, followed by the sequence of the 36 amino acid human pancreatic polypeptide, which again is separated from the human pancreatic icosapeptide sequence by a classic cleavage and amidation site, Gly-Lys-Arg. The precursor terminates in a heptapeptide which is cleaved from the icosapeptide at a monobasic processing site. Both the size and the structure of the PP precursor was supported by the results of peptide analysis of biosynthetically labeled pro-PP isolated from canine PP cells in which processing was prevented by the arginine analogue canavanine. It is concluded that the precursor for mammalian PP gives rise to two peptide products, the well preserved, carboxyamidated PP and an icosapeptide which is preserved only in its COOH-terminal end, plus a small highly variable COOH-terminal oligopeptide.

Full text

PDF
909

Images in this article

910Fig. 3.
on p.910

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Attias J., Schlesinger M. J., Schlesinger S. The effect of amino acid analogues on alkaline phosphatase formation in Escherichia coli K-12. IV. Substitution of canavanine for arginine. J Biol Chem. 1969 Jul 25;244(14):3810–3817. [PubMed] [Google Scholar]
  2. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boel E., Vuust J., Norris F., Norris K., Wind A., Rehfeld J. F., Marcker K. A. Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication. Proc Natl Acad Sci U S A. 1983 May;80(10):2866–2869. doi: 10.1073/pnas.80.10.2866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bradbury A. F., Finnie M. D., Smyth D. G. Mechanism of C-terminal amide formation by pituitary enzymes. Nature. 1982 Aug 12;298(5875):686–688. doi: 10.1038/298686a0. [DOI] [PubMed] [Google Scholar]
  5. Casadaban M. J., Cohen S. N. Analysis of gene control signals by DNA fusion and cloning in Escherichia coli. J Mol Biol. 1980 Apr;138(2):179–207. doi: 10.1016/0022-2836(80)90283-1. [DOI] [PubMed] [Google Scholar]
  6. Gates R. J., Lazarus N. R. The ability of pancreatic polypeptides (APP and BPP) to return to normal the hyperglycaemia, hyperinsulinaemia and weight gain of New Zealand obese mice. Horm Res. 1977;8(4):189–202. doi: 10.1159/000178800. [DOI] [PubMed] [Google Scholar]
  7. Gergen J. P., Stern R. H., Wensink P. C. Filter replicas and permanent collections of recombinant DNA plasmids. Nucleic Acids Res. 1979 Dec 20;7(8):2115–2136. doi: 10.1093/nar/7.8.2115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Halban P. A. Inhibition of proinsulin to insulin conversion in rat islets using arginine and lysine analogs. Lack of effect on rate of release of modified products. J Biol Chem. 1982 Nov 25;257(22):13177–13180. [PubMed] [Google Scholar]
  9. Kimmel J. R., Hayden L. J., Pollock H. G. Isolation and characterization of a new pancreatic polypeptide hormone. J Biol Chem. 1975 Dec 25;250(24):9369–9376. [PubMed] [Google Scholar]
  10. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  11. Larsson L. I., Boder G. B., Shaw W. N. Changes in the islets of langerhans in the obese Zucker rat. Lab Invest. 1977 Jun;36(6):593–598. [PubMed] [Google Scholar]
  12. Larsson L. I., Sundler F., Håkanson R. Pancreatic polypeptide - a postulated new hormone: identification of its cellular storage site by light and electron microscopic immunocytochemistry. Diabetologia. 1976 Jul;12(3):211–226. doi: 10.1007/BF00422088. [DOI] [PubMed] [Google Scholar]
  13. Malaisse-Lagae F., Carpentier J. L., Patel Y. C., Malaisse W. J., Orci L. Pancreatic polypeptide: a possible role in the regulation of food intake in the mouse. Hypothesis. Experientia. 1977 Jul 15;33(7):915–917. doi: 10.1007/BF01951279. [DOI] [PubMed] [Google Scholar]
  14. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Noe B. D. Inhibition of islet prohormone to hormone conversion by incorporation of arginine and lysine analogs. J Biol Chem. 1981 May 25;256(10):4940–4946. [PubMed] [Google Scholar]
  16. Pines M., Rosenthal G. A., Applebaum S. W. In vitro incorporation of L-canavanine into vitellogenin of the fat body of the migratory locust Locusta migratoria migratorioides. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5480–5483. doi: 10.1073/pnas.78.9.5480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schwartz T. W., Gingerich R. L., Tager H. S. Biosynthesis of pancreatic polypeptide. Identification of a precursor and a co-synthesized product. J Biol Chem. 1980 Dec 10;255(23):11494–11498. [PubMed] [Google Scholar]
  18. Schwartz T. W. Pancreatic polypeptide: a hormone under vagal control. Gastroenterology. 1983 Dec;85(6):1411–1425. [PubMed] [Google Scholar]
  19. Schwartz T. W., Tager H. S. Isolation and biogenesis of a new peptide from pancreatic islets. Nature. 1981 Dec 10;294(5841):589–591. doi: 10.1038/294589a0. [DOI] [PubMed] [Google Scholar]
  20. Steiner D. F., Quinn P. S., Chan S. J., Marsh J., Tager H. S. Processing mechanisms in the biosynthesis of proteins. Ann N Y Acad Sci. 1980;343:1–16. doi: 10.1111/j.1749-6632.1980.tb47238.x. [DOI] [PubMed] [Google Scholar]
  21. Tatemoto K. Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2514–2518. doi: 10.1073/pnas.79.8.2514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tatemoto K. Neuropeptide Y: complete amino acid sequence of the brain peptide. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5485–5489. doi: 10.1073/pnas.79.18.5485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zipf W. B., O'Dorisio T. M., Cataland S., Sotos J. Blunted pancreatic polypeptide responses in children with obesity of Prader-Willi syndrome. J Clin Endocrinol Metab. 1981 Jun;52(6):1264–1266. doi: 10.1210/jcem-52-6-1264. [DOI] [PubMed] [Google Scholar]
  24. von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983 Jun 1;133(1):17–21. doi: 10.1111/j.1432-1033.1983.tb07424.x. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES