THE FAMILY OF SUBTILISIN/KEXIN LIKE PRO-PROTEIN AND PROHORMONE CONVERTASES - DIVERGENT OR SHARED FUNCTIONS
THE FAMILY OF SUBTILISIN/KEXIN LIKE PRO-PROTEIN AND PROHORMONE CONVERTASES - DIVERGENT OR SHARED FUNCTIONS
复制标题
DOI：
10.1016/0300-9084(94)90147-3
复制
发表时间：
1994-01-01
期刊：
影响因子：
3.9
通讯作者：
DAY, R
中科院分区：
文献类型：
--
作者：
SEIDAH, N;CHRETIEN, M;DAY, R
最近发现了六种哺乳动物加工酶，它们与酵母kexin和细菌枯草杆菌蛋白酶具有显著的相似性。这些枯草杆菌蛋白酶/kexin样转化酶被称为furin/PACE、PC 1/PC 3、PC 2、PACE 4、PC 4和PC 5/PC6。通过北方印迹分析这些转化酶在大鼠组织和细胞系中的mRNA表达的分析证明了每种酶的独特模式。因此，尽管弗林蛋白酶和PACE 4 mRNA（各4.4kb）表现出广泛的组织分布，但只有弗林蛋白酶普遍表达。PACE 4主要表现为4.4 kb的mRNA形式，在某些组织中检测到3.9 kb的形式。PC 5 mRNA（主要为3.8 kb）在其分布上比PACE 4和弗林蛋白酶更受限制，并且它表现出多种mRNA形式的存在，导致C末端富含Cys结构域的长度可变。此外，与弗林蛋白酶和PACE 4一样，PC 5在调节型和组成型分泌细胞中表达。相反，PC 1（3和5 kb）和PC 2（2.8和5 kb）主要在含有分泌颗粒的组织和细胞中表达。还检测到多种mRNA形式，但就目前所知，它们都不影响其开放阅读框，仅导致3'非编码序列的长度可变。最后，PC 4 mRNA（2.8 kb主要和1.9 kb次要）仅在睾丸生殖细胞中表达。对PC 1和PC 2的酶原激活及其与许多前体细胞共表达后的切割特异性的生物合成分析表明，尽管pro-PC 1在内质网中被快速激活为PC 1，但pro-PC 2转化为PC 2相当缓慢。pro-PC 2裂解成PC 2开始于transGolgi网络，并由称为7 B2的内源性内分泌和神经前体调节。虽然转化酶基因的遗传结构非常相似，但它们表现出独特的启动子序列，并且只有弗林蛋白酶和PACE 4基因位于同一染色体上。
Six mammalian processing enzymes were recently discovered which exhibit significant similarities to both yeast kexin and bacterial subtilisins. These subtilisin/kexin-like convertases were called furin/PACE, PC1/PC3, PC2, PACE4, PC4 and PC5/PC6. The analysis of the mRNA expression of these convertases in rat tissues and cell lines by Northern blot analysis demonstrated a unique pattern for each enzyme. Thus, although furin and PACE4 mRNA (4.4 kb each) exhibit a widespread tissue distribution only furin is ubiquitously expressed. PACE4 exhibits a major 4.4 kb mRNA form, and in some tissues a 3.9 kb form is detected. PC5 mRNA (3.8 kb major) is more restricted in its distribution than PACE4 and furin, and it exhibits the presence of multiple mRNA forms, resulting in variable lengths of the C-terminal Cys-rich domain. In addition, like furin and PACE4, PC5 is expressed in both regulated and constitutively secreting cells. In contrast, PC1 (3 and 5 kb) and PC2 (2.8 and 5 kb) are primarily expressed in tissues and cells containing secretory granules. Multiple mRNA forms are also detected, but as far as is known none affect their open reading frame and only result in a variable length of the 3' non-coding sequence. Finally, PC4 mRNA (2.8 kb major and 1.9 kb minor) is only expressed in testicular germ cells. Biosynthetic analysis of the zymogen activation of PC1 and PC2 and their cleavage specificity following their cellular co-expression with a number of precursors, demonstrated that although pro-PC 1 is rapidly activated to PC1 in the endoplasmic reticulum, pro-PC2 conversion into PC2 is rather slow. The cleavage of pro-PC2 into PC2 starts in the trans Golgi network and is regulated by an endogenous endocrine and neural precursor called 7B2. Although the genetic organization of the convertase genes is very similar, they exhibit unique promoter sequences and only furin and PACE4 genes are localized on the same chromosome.