Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem

P. K. Lund, Richard Goodman, P. C. Dee, J. F. Habener

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

We have constructed and cloned in bacteria recombinant plasmids containing DNA complementary to the mRNA encoding a pancreatic preproglucagon (M(r) 14,500), a product of cell-free translation of angler fish islet mRNAs shown previously by immunoprecipitation analyses to be a precursor of glucagon. cDNAs of 630, 180, and 120 base pairs were isolated and correspond to most of the mRNA for the preproglucagon (650 bases). The cDNAs contain a protein coding sequence of 372 nucleotides and 5'- and 3'-untranslated regions of 58 and 206 nucleotides, respectively. From the coding sequence of the cDNAs, we find that the sequence of glucagon, identical to mammalian glucagon in 20 of 29 positions, resides in the preproglucagon of 124 amino acids flanked by NH2- and COOH-peptide extensions of 52 and 43 amino acids, respectively. The peptide extensions are linked to the glucagon by Lys-Arg sequences characteristic of the sites that are cleaved during the posttranslational processing of prohormones. Notable is the finding that, following the initial Lys-Arg sequence in the COOH-peptide extension is a pentapeptide, Ser-Gly-Val-Ala-Glu, followed by another Lys-Arg and a sequence of 34 residues that shows striking homology with glucagon and the other peptides of the glucagon family-gastric inhibitory peptide, vasoactive intestinal peptide, and secretin. Thus, the preproglucagon mRNA contains two glucagon-related coding sequences arranged in tandem. The finding of Lys-Arg sequences flanking the glucagon and glucagon-related sequences suggests that these two peptides and a pentapeptide are formed in vivo by posttranslational cleavages of a common precursor.

Original languageEnglish (US)
Pages (from-to)345-349
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume79
Issue number2 I
StatePublished - 1982
Externally publishedYes

Fingerprint

Proglucagon
Glucagon
Complementary DNA
Peptides
Messenger RNA
Amino Acids
Secretin
5' Untranslated Regions
Vasoactive Intestinal Peptide
3' Untranslated Regions
Immunoprecipitation
Base Pairing
Stomach
Fishes
Plasmids
Nucleotides
Bacteria

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem. / Lund, P. K.; Goodman, Richard; Dee, P. C.; Habener, J. F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 79, No. 2 I, 1982, p. 345-349.

Research output: Contribution to journalArticle

@article{a04a2241cd4a4a8b95fd6f3f2f60714d,
title = "Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem",
abstract = "We have constructed and cloned in bacteria recombinant plasmids containing DNA complementary to the mRNA encoding a pancreatic preproglucagon (M(r) 14,500), a product of cell-free translation of angler fish islet mRNAs shown previously by immunoprecipitation analyses to be a precursor of glucagon. cDNAs of 630, 180, and 120 base pairs were isolated and correspond to most of the mRNA for the preproglucagon (650 bases). The cDNAs contain a protein coding sequence of 372 nucleotides and 5'- and 3'-untranslated regions of 58 and 206 nucleotides, respectively. From the coding sequence of the cDNAs, we find that the sequence of glucagon, identical to mammalian glucagon in 20 of 29 positions, resides in the preproglucagon of 124 amino acids flanked by NH2- and COOH-peptide extensions of 52 and 43 amino acids, respectively. The peptide extensions are linked to the glucagon by Lys-Arg sequences characteristic of the sites that are cleaved during the posttranslational processing of prohormones. Notable is the finding that, following the initial Lys-Arg sequence in the COOH-peptide extension is a pentapeptide, Ser-Gly-Val-Ala-Glu, followed by another Lys-Arg and a sequence of 34 residues that shows striking homology with glucagon and the other peptides of the glucagon family-gastric inhibitory peptide, vasoactive intestinal peptide, and secretin. Thus, the preproglucagon mRNA contains two glucagon-related coding sequences arranged in tandem. The finding of Lys-Arg sequences flanking the glucagon and glucagon-related sequences suggests that these two peptides and a pentapeptide are formed in vivo by posttranslational cleavages of a common precursor.",
author = "Lund, {P. K.} and Richard Goodman and Dee, {P. C.} and Habener, {J. F.}",
year = "1982",
language = "English (US)",
volume = "79",
pages = "345--349",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "2 I",

}

TY - JOUR

T1 - Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem

AU - Lund, P. K.

AU - Goodman, Richard

AU - Dee, P. C.

AU - Habener, J. F.

PY - 1982

Y1 - 1982

N2 - We have constructed and cloned in bacteria recombinant plasmids containing DNA complementary to the mRNA encoding a pancreatic preproglucagon (M(r) 14,500), a product of cell-free translation of angler fish islet mRNAs shown previously by immunoprecipitation analyses to be a precursor of glucagon. cDNAs of 630, 180, and 120 base pairs were isolated and correspond to most of the mRNA for the preproglucagon (650 bases). The cDNAs contain a protein coding sequence of 372 nucleotides and 5'- and 3'-untranslated regions of 58 and 206 nucleotides, respectively. From the coding sequence of the cDNAs, we find that the sequence of glucagon, identical to mammalian glucagon in 20 of 29 positions, resides in the preproglucagon of 124 amino acids flanked by NH2- and COOH-peptide extensions of 52 and 43 amino acids, respectively. The peptide extensions are linked to the glucagon by Lys-Arg sequences characteristic of the sites that are cleaved during the posttranslational processing of prohormones. Notable is the finding that, following the initial Lys-Arg sequence in the COOH-peptide extension is a pentapeptide, Ser-Gly-Val-Ala-Glu, followed by another Lys-Arg and a sequence of 34 residues that shows striking homology with glucagon and the other peptides of the glucagon family-gastric inhibitory peptide, vasoactive intestinal peptide, and secretin. Thus, the preproglucagon mRNA contains two glucagon-related coding sequences arranged in tandem. The finding of Lys-Arg sequences flanking the glucagon and glucagon-related sequences suggests that these two peptides and a pentapeptide are formed in vivo by posttranslational cleavages of a common precursor.

AB - We have constructed and cloned in bacteria recombinant plasmids containing DNA complementary to the mRNA encoding a pancreatic preproglucagon (M(r) 14,500), a product of cell-free translation of angler fish islet mRNAs shown previously by immunoprecipitation analyses to be a precursor of glucagon. cDNAs of 630, 180, and 120 base pairs were isolated and correspond to most of the mRNA for the preproglucagon (650 bases). The cDNAs contain a protein coding sequence of 372 nucleotides and 5'- and 3'-untranslated regions of 58 and 206 nucleotides, respectively. From the coding sequence of the cDNAs, we find that the sequence of glucagon, identical to mammalian glucagon in 20 of 29 positions, resides in the preproglucagon of 124 amino acids flanked by NH2- and COOH-peptide extensions of 52 and 43 amino acids, respectively. The peptide extensions are linked to the glucagon by Lys-Arg sequences characteristic of the sites that are cleaved during the posttranslational processing of prohormones. Notable is the finding that, following the initial Lys-Arg sequence in the COOH-peptide extension is a pentapeptide, Ser-Gly-Val-Ala-Glu, followed by another Lys-Arg and a sequence of 34 residues that shows striking homology with glucagon and the other peptides of the glucagon family-gastric inhibitory peptide, vasoactive intestinal peptide, and secretin. Thus, the preproglucagon mRNA contains two glucagon-related coding sequences arranged in tandem. The finding of Lys-Arg sequences flanking the glucagon and glucagon-related sequences suggests that these two peptides and a pentapeptide are formed in vivo by posttranslational cleavages of a common precursor.

UR - http://www.scopus.com/inward/record.url?scp=0020026919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020026919&partnerID=8YFLogxK

M3 - Article

C2 - 7043459

AN - SCOPUS:0020026919

VL - 79

SP - 345

EP - 349

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 2 I

ER -