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EMBO J. 1984 Apr; 3(4): 909–912.





PMCID: PMC557446

PMID: 6373251



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




E Boel, T W Schwartz, K E Norris, and N P Fiil




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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.



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Selected References


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

  • Attias J, Schlesinger MJ, 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]

  • Birnboim HC, Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. [PMC free article] [PubMed]

  • Boel E, Vuust J, Norris F, Norris K, Wind A, Rehfeld JF, Marcker KA. 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. [PMC free article] [PubMed]

  • Bradbury AF, Finnie MD, Smyth DG. Mechanism of C-terminal amide formation by pituitary enzymes. Nature. 1982 Aug 12;298(5875):686–688. [PubMed]

  • Casadaban MJ, Cohen SN. Analysis of gene control signals by DNA fusion and cloning in Escherichia coli. J Mol Biol. 1980 Apr;138(2):179–207. [PubMed]

  • Gates RJ, Lazarus NR. 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. [PubMed]

  • Gergen JP, Stern RH, Wensink PC. Filter replicas and permanent collections of recombinant DNA plasmids. Nucleic Acids Res. 1979 Dec 20;7(8):2115–2136. [PMC free article] [PubMed]

  • Halban PA. 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]

  • Kimmel JR, Hayden LJ, Pollock HG. Isolation and characterization of a new pancreatic polypeptide hormone. J Biol Chem. 1975 Dec 25;250(24):9369–9376. [PubMed]

  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]

  • Larsson LI, 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. [PubMed]

  • Larsson LI, Boder GB, Shaw WN. Changes in the islets of langerhans in the obese Zucker rat. Lab Invest. 1977 Jun;36(6):593–598. [PubMed]

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  • Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. [PMC free article] [PubMed]

  • Noe BD. 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]

  • Pines M, Rosenthal GA, Applebaum SW. 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. [PMC free article] [PubMed]

  • Schwartz TW. Pancreatic polypeptide: a hormone under vagal control. Gastroenterology. 1983 Dec;85(6):1411–1425. [PubMed]

  • Schwartz TW, Tager HS. Isolation and biogenesis of a new peptide from pancreatic islets. Nature. 1981 Dec 10;294(5841):589–591. [PubMed]

  • Schwartz TW, Gingerich RL, Tager HS. Biosynthesis of pancreatic polypeptide. Identification of a precursor and a co-synthesized product. J Biol Chem. 1980 Dec 10;255(23):11494–11498. [PubMed]

  • Steiner DF, Quinn PS, Chan SJ, Marsh J, Tager HS. Processing mechanisms in the biosynthesis of proteins. Ann N Y Acad Sci. 1980;343:1–16. [PubMed]

  • 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. [PMC free article] [PubMed]

  • 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. [PMC free article] [PubMed]

  • von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983 Jun 1;133(1):17–21. [PubMed]

  • Zipf WB, O'Dorisio TM, 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. [PubMed]




Associated Data


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An external file that holds a picture, illustration, etc.Object name is emboj00308-0210.tif" title="An external file that holds a picture, illustration, etc."
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Object name is emboj00308-0211.tif" src="/pmc/articles/PMC557446/bin/emboj00308-0211.tif"/>






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