Blackstone C D, Seino S, Takeuchi T, Yamada T, Steiner D F
Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637.
J Biol Chem. 1988 Feb 25;263(6):2911-6.
Studies on New World hystricomorph rodents have revealed interesting structural divergences in the peptide hormones of the islets of Langerhans, particularly with respect to insulin and glucagon. Herein we report the isolation and sequencing of a cDNA encoding the precursor of pancreatic polypeptide (PP) from a guinea pig pancreas cDNA library. The 126-residue precursor sequence is predicted to include a 26-residue NH2-terminal signal peptide followed by the 36-amino acid PP hormonal sequence and a large COOH-terminal extension. The sequence identity between guinea pig and human PP is 89% (32/36 residues), and the predicted sequence is in agreement with that reported by Eng et al. (Eng, J., Huang, C.-G., Pan, Y.-C. E., Hulmes, J. D., and Yalow, R. S. (1987) Peptides 8, 165-168). In contrast, the icosapeptide domain in the guinea pig precursor exhibits only 40% (8/20) identity with the corresponding human precursor domain, and the COOH-terminal extension differs greatly in both sequence and size. The guinea pig precursor lacks the monobasic processing site (Pro-Arg) found at the COOH terminus of the icosapeptide domain in human, ovine, canine, and feline proPP. An icosapeptide is thus not likely to be liberated as such from this precursor. Of particular interest in guinea pig proPP is the substitution of serine for arginine at the dibasic amino acid processing site on the COOH-terminal side of the PP domain. Results of radioimmunoassays of gel-filtered protein fractions from a guinea pig pancreas extract indicate that efficient proteolytic cleavage takes place at this Lys-Ser site and that mature guinea pig PP is normally carboxyamidated.
对新大陆豪猪亚目啮齿动物的研究揭示了胰岛肽激素中有趣的结构差异，特别是在胰岛素和胰高血糖素方面。在此，我们报告了从豚鼠胰腺cDNA文库中分离并测序编码胰多肽（PP）前体的cDNA。126个氨基酸残基的前体序列预计包括一个26个氨基酸残基的NH2末端信号肽，随后是36个氨基酸的PP激素序列和一个大的COOH末端延伸。豚鼠和人PP之间的序列同一性为89%（32/36个残基），预测序列与Eng等人报道的一致（Eng, J., Huang, C.-G., Pan, Y.-C. E., Hulmes, J. D., and Yalow, R. S. (1987) Peptides 8, 165 - 168）。相比之下，豚鼠前体中的二十肽结构域与相应的人前体结构域仅显示40%（8/20）的同一性，并且COOH末端延伸在序列和大小上都有很大差异。豚鼠前体缺乏在人、羊、犬和猫的proPP的二十肽结构域COOH末端发现的单碱性加工位点（Pro-Arg）。因此，不太可能从该前体中释放出这样的二十肽。豚鼠proPP中特别有趣的是在PP结构域COOH末端的双碱性氨基酸加工位点处精氨酸被丝氨酸取代。来自豚鼠胰腺提取物的凝胶过滤蛋白组分的放射免疫分析结果表明，在这个Lys-Ser位点发生了有效的蛋白水解切割，并且成熟的豚鼠PP通常是羧基酰胺化的。
