Benjannet S, Rondeau N, Day R, Chrétien M, Seidah N G
J. A. DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, PQ, Canada.
Proc Natl Acad Sci U S A. 1991 May 1;88(9):3564-8. doi: 10.1073/pnas.88.9.3564.
A recombinant vaccinia virus vector was used to coexpress the two candidate mouse prohormone convertases, PC1 and PC2, together with mouse proopiomelanocortin (POMC) in the constitutively secreting cell line BSC-40 and in the endocrine tissue-derived cell lines PC12 and AtT-20, which exhibit regulated secretion. Monitoring of POMC processing demonstrated the distinct cleavage specificities of PC1 and PC2, since in the cell lines analyzed (i) PC1 cleaves POMC into corticotropin and beta-lipotropin, (ii) PC2 cleaves POMC into beta-endorphin, an N-terminally extended corticotropin containing the joining peptide, and either alpha MSH or desacetyl-alpha MSH, and (iii) PC2 cleaves POMC at the five pairs of basic residues analyzed, whereas PC1 cleaves two of them preferentially, suggesting that PC2 has a broader spectrum of activity than PC1. These data are consistent with our hypothesis on the physiological role of PC1 and PC2 as distinct proprotein convertases acting alone or together to produce a set of tissue-specific maturation products in the brain and in peripheral tissues.
一种重组痘苗病毒载体被用于在持续分泌的细胞系BSC-40以及表现出调节性分泌的内分泌组织来源的细胞系PC12和AtT-20中，与小鼠阿黑皮素原（POMC）一起共表达两种候选小鼠激素原转化酶PC1和PC2。对POMC加工过程的监测表明了PC1和PC2不同的切割特异性，因为在所分析的细胞系中：（i）PC1将POMC切割成促肾上腺皮质激素和β-促脂素；（ii）PC2将POMC切割成β-内啡肽、一种包含连接肽的N端延伸的促肾上腺皮质激素以及α-促黑素细胞激素（α-MSH）或去乙酰-α-促黑素细胞激素（desacetyl-α-MSH）；（iii）PC2在所分析的五对碱性残基处切割POMC，而PC1优先切割其中两对，这表明PC2比PC1具有更广泛的活性谱。这些数据与我们关于PC1和PC2作为不同的前体蛋白转化酶在大脑和外周组织中单独或共同作用以产生一组组织特异性成熟产物的生理作用的假设一致。
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