PC1 AND PC2 ARE PROPROTEIN CONVERTASES CAPABLE OF CLEAVING PROOPIOMELANOCORTIN AT DISTINCT PAIRS OF BASIC RESIDUES
PC1 AND PC2 ARE PROPROTEIN CONVERTASES CAPABLE OF CLEAVING PROOPIOMELANOCORTIN AT DISTINCT PAIRS OF BASIC RESIDUES
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DOI：
10.1073/pnas.88.9.3564
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发表时间：
1991-05-01
影响因子：
11.1
通讯作者：
SEIDAH, NG
中科院分区：
文献类型：
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作者：
BENJANNET, S;RONDEAU, N;SEIDAH, NG
利用重组痘苗病毒载体，将两种候选小鼠前激素转换酶PC1和PC2与小鼠前阿片黑素皮质素(POMC)在分泌细胞系BSC-40和内分泌组织源细胞系PC12和AtT20中共表达。对POMC加工的监测表明，PC1和PC2具有明显的切割特异性，因为在所分析的细胞系中，(I)PC1将POMC裂解为促肾上腺皮质激素和β-促脂激素，(Ii)PC2将POMC裂解为β-内啡肽，一个N端延伸的促肾上腺皮质激素，含有连接肽，以及α-MSH或去乙酰基-α-MSH，以及(Iii)PC2在所分析的五对碱性残基上裂解POMC，而PC1优先裂解其中两对，这表明PC2具有比PC1更广泛的活性谱。这些数据与我们的假设一致，即PC1和PC2作为不同的原蛋白转换酶单独或共同作用，在大脑和周围组织中产生一系列组织特异性成熟产物的生理作用。
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 AtT20, 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.