前激素转化酶对分泌粒蛋白II的加工：PC1在分泌神经肽生成中的重要性。

Processing of secretogranin II by prohormone convertases: importance of PC1 in generation of secretoneurin.

作者信息

Hoflehner J, Eder U, Laslop A, Seidah N G, Fischer-Colbrie R, Winkler H

机构信息

Department of Pharmacology, University of Innsbruck, Austria.

出版信息

FEBS Lett. 1995 Mar 6;360(3):294-8. doi: 10.1016/0014-5793(95)00127-u.

DOI:10.1016/0014-5793(95)00127-u

PMID:7883050

Abstract

Secretoneurin is a recently characterized neuropeptide present in the primary amino acid sequence of secretogranin II. We investigated the proteolytic processing of secretogranin II by prohormone convertases in vivo in a cellular system using the vaccinia virus system. Both PC1 and PC2 can cleave the secretogranin II precursor at sites of pairs of basic amino acids to yield intermediate-sized fragments. Other convertases like PACE4, PC5 and furin were not active. For the formation of the free neuropeptide secretoneurin a different pattern was found. Only PC1 but none of the other convertases tested including PC2 were capable of generating secretoneurin. Our results demonstrate that the prohormone convertases PC1 and PC2 are involved in proteolytic processing of secretogranin II. The neuropeptide secretoneurin can only be generated by PC1 suggesting tissue-specific processing of secretogranin II in neurons expressing different subsets of the prohormone convertases.

摘要

促分泌素原神经肽是最近在分泌粒蛋白II的一级氨基酸序列中发现的一种神经肽。我们利用痘苗病毒系统，在细胞体系中对促激素转化酶在体内对分泌粒蛋白II的蛋白水解加工过程进行了研究。PC1和PC2均可在成对碱性氨基酸位点切割分泌粒蛋白II前体，产生中等大小的片段。其他转化酶如PACE4、PC5和弗林蛋白酶则无活性。对于游离神经肽促分泌素原神经肽的形成，发现了不同的模式。只有PC1能够生成促分泌素原神经肽，而包括PC2在内的其他所测试的转化酶均不能生成。我们的结果表明，激素原转化酶PC1和PC2参与了分泌粒蛋白II的蛋白水解加工过程。神经肽促分泌素原神经肽只能由PC1生成，这表明在表达不同激素原转化酶亚型的神经元中，分泌粒蛋白II存在组织特异性加工过程。