Exons of the human pancreatic polypeptide gene define functional domains of the precursor.

作者: A B Leiter , M R Montminy , E Jamieson , R H Goodman

DOI: 10.1016/S0021-9258(17)38830-0

关键词: ExonSignal peptideBiologyGenePancreatic polypeptideUntranslated regionMolecular biologyNucleic acid sequenceComplementary DNARFX6Cell biologyBiochemistry

摘要: Abstract Pancreatic polypeptide is a 36-amino acid peptide which inhibits pancreatic exocrine function. We have previously determined from the nucleotide sequence of cDNA that derived 95-amino precursor, prepropancreatic polypeptide. Pulse-chase studies suggested precursor cleaved to produce three peptides: polypeptide, an icosapeptide, and smaller peptide. In present study, we used cloned as hybridization probe isolate gene human bacteriophage genomic library. The 2.8 kilobases DNA representing entire was determined. contains four exons introns. Exon 1 encodes 5'-untranslated region mRNA, exon 2 signal 3 4 carboxyl-terminal heptapeptide 3'-untranslated mRNA. By Southern blot analysis, detected in polypeptide-producing islet cell tumor indistinguishable normal leukocytes. structure consistent with hypothesis generates distinct peptides, each encoded by separate exon. Increased expression does not appear be correlated major alterations structure.

参考文章(31)
E. Boel, T.W. Schwartz, K.E. Norris, N.P. Fiil, A cDNA encoding a small common precursor for human pancreatic polypeptide and pancreatic icosapeptide. The EMBO Journal. ,vol. 3, pp. 909- 912 ,(1984) , 10.1002/J.1460-2075.1984.TB01904.X
A B Leiter, H T Keutmann, R H Goodman, Structure of a precursor to human pancreatic polypeptide. Journal of Biological Chemistry. ,vol. 259, pp. 14702- 14705 ,(1984) , 10.1016/S0021-9258(17)42659-7
T.W. Schwartz, R.L. Gingerich, H.S. Tager, Biosynthesis of pancreatic polypeptide. Identification of a precursor and a co-synthesized product. Journal of Biological Chemistry. ,vol. 255, pp. 11494- 11498 ,(1980) , 10.1016/S0021-9258(19)70318-4
G Heinrich, P Gros, J F Habener, Glucagon gene sequence. Four of six exons encode separate functional domains of rat pre-proglucagon. Journal of Biological Chemistry. ,vol. 259, pp. 14082- 14087 ,(1984) , 10.1016/S0021-9258(18)89859-3
R.H. Goodman, J.W. Jacobs, P.C. Dee, J.F. Habener, Somatostatin-28 encoded in a cloned cDNA obtained from a rat medullary thyroid carcinoma. Journal of Biological Chemistry. ,vol. 257, pp. 1156- 1159 ,(1982) , 10.1016/S0021-9258(19)68167-6
R J Deschenes, R S Haun, C L Funckes, J E Dixon, A gene encoding rat cholecystokinin. Isolation, nucleotide sequence, and promoter activity. Journal of Biological Chemistry. ,vol. 260, pp. 1280- 1286 ,(1985) , 10.1016/S0021-9258(20)71240-8
H Weiher, M Konig, P Gruss, Multiple point mutations affecting the simian virus 40 enhancer. Science. ,vol. 219, pp. 626- 631 ,(1983) , 10.1126/SCIENCE.6297005
Thue W. Schwartz, Howard S. Tager, Isolation and biogenesis of a new peptide from pancreatic islets Nature. ,vol. 294, pp. 589- 591 ,(1981) , 10.1038/294589A0
A. M. Maxam, W. Gilbert, A new method for sequencing DNA Proceedings of the National Academy of Sciences of the United States of America. ,vol. 74, pp. 560- 564 ,(1977) , 10.1073/PNAS.74.2.560