Parker D B, Coe I R, Dixon G H, Sherwood N M
Department of Biology, University of Victoria, Canada.
Eur J Biochem. 1993 Jul 15;215(2):439-48. doi: 10.1111/j.1432-1033.1993.tb18051.x.
A cDNA that codes for two peptides in the glucagon superfamily has been isolated from sockeye salmon brain. The first peptide is related to growth hormone-releasing hormone (GHRH), which has high sequence similarity with PACAP-related peptide. The second peptide is structurally related to vasoactive intestinal peptide, which is also related to a newly identified peptide in mannals, pituitary adenylate-cyclase-activating polypeptide (PACAP). The salmon precursor contains 173 amino acids and has dibasic and monobasic enzyme-processing sites for cleavage of a 45-amino-acid GHRH-like peptide with a free C-terminus and a 38-amino-acid PACAP with an amidated C-terminus. The salmon GHRH-like peptide has 40% amino acid sequence identity with a human GHRH and 56% identity with human PACAP-related peptide. The 38-amino-acid salmon PACAP is highly conserved (89-92% identity) with only three or four amino acid substitutions compared with the human, ovine and rat 38-amino-acid PACAP. Not previously reported for mammalian species, a short precursor coding for only one peptide exists in salmon in addition to the long precursor coding for two peptides. In the short precursor, the coding region for GHRH is deleted leaving the PACAP-coding region in a correct reading frame. This provides one possible control mechanism for an increased expression of one peptide (PACAP) without the concomitant increase in the other peptide (GHRH) as occurs in a double-peptide precursor. The importance of the 3' non-translated region of the salmon GHRH/PACAP precursor in the regulation of translation is suggested by its 70% nucleotide sequence identity to the 3' non-translated regions of the mammalian PACAP precursors. The structural organization of the salmon GHRH/PACAP precursor provides a possible evolutionary scheme for precursors that contain tandem peptides in the glucagon superfamily.
从红大马哈鱼脑中分离出了一种编码胰高血糖素超家族中两种肽的互补DNA（cDNA）。第一种肽与生长激素释放激素（GHRH）相关，它与垂体腺苷酸环化酶激活肽相关肽（PACAP）具有高度的序列相似性。第二种肽在结构上与血管活性肠肽相关，血管活性肠肽也与哺乳动物中一种新发现的肽——垂体腺苷酸环化酶激活多肽（PACAP）相关。鲑鱼前体包含173个氨基酸，具有双碱性和单碱性酶切加工位点，可切割出一个具有游离C末端的45个氨基酸的类GHRH肽和一个具有酰胺化C末端的38个氨基酸的PACAP。鲑鱼类GHRH肽与人类GHRH的氨基酸序列一致性为40%，与人类PACAP相关肽的一致性为56%。与人类、绵羊和大鼠的38个氨基酸的PACAP相比，38个氨基酸的鲑鱼PACAP高度保守（一致性为89 - 92%），只有三到四个氨基酸替换。除了编码两种肽的长前体之外，鲑鱼中还存在一种仅编码一种肽的短前体，这在哺乳动物物种中尚未有报道。在短前体中，GHRH的编码区域被删除，使PACAP编码区域处于正确的阅读框中。这为一种肽（PACAP）表达增加而另一种肽（GHRH）不随之增加提供了一种可能的控制机制，就像在双肽前体中发生的那样。鲑鱼GHRH/PACAP前体3'非翻译区与哺乳动物PACAP前体3'非翻译区70%的核苷酸序列一致性表明了其在翻译调控中的重要性。鲑鱼GHRH/PACAP前体的结构组织为胰高血糖素超家族中包含串联肽的前体提供了一种可能的进化模式。
