The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone
The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone
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生殖细胞特异性 PCSK4 蛋白酶的前体在转染的体细胞中被低效激活：与 BiP 伴侣相互作用的证据
DOI：
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发表时间：
2011
影响因子：
4.3
通讯作者：
M. Mbikay
中科院分区：
文献类型：
--
作者：
Charles Gyamera;F. Sirois;Nicholas J. Denis;P. Mishra;D. Figeys;A. Basak;M. Mbikay
前蛋白转化酶枯草杆菌蛋白酶/kexin 4型（PCSK 4），也称为前蛋白转化酶4（PC 4），是一种丝氨酸内切蛋白酶，主要在睾丸生殖细胞和精子中表达。其基因在小鼠中失活导致雄性不育。从PCSK 3/弗林蛋白酶（其最近的亲戚）的生物合成的研究中，已经推断PCSK 4在内质网中作为酶原合成;它通过前结构域和催化结构域之间的自催化切割而迅速成熟;切割的前结构域保持附着于成熟酶;并且该酶最终通过在前结构域内二次切割后除去前结构域肽而被激活。在这项研究中，我们使用人胚肾293（HEK 293）细胞来研究大鼠或人PCSK 4的生物合成。我们的研究结果表明，大部分的PCSK 4仍然作为细胞内酶原，大概被困在内质网，在那里它与一般的分子伴侣葡萄糖调节蛋白78/免疫球蛋白重链结合蛋白（GRP 78/BiP）相互作用。这些数据表明，与转化酶家族的其他成员不同，proPCSK 4不能在体细胞中有效地自我激活。这些细胞可能缺乏细胞内环境和睾丸生殖细胞特异性的相互作用分子，而睾丸生殖细胞通常表达这种酶。
Proprotein convertase subtilisin/kexin type 4 (PCSK4), also known as proprotein convertase 4 (PC4), is a serine endoproteinase primarily expressed in testicular germ cells and in sperm. Inactivation of its gene in mouse causes male infertility. From studies of the biosynthesis of PCSK3/furin, its closest relative, it has been inferred that PCSK4 is synthesised in the endoplasmic reticulum as a zymogen; that it is rapidly matured by autocatalytic cleavage between the prodomain and the catalytic domain; that the cleaved prodomain remains attached to the mature enzyme; and that the enzyme is finally activated by the removal of the prodomain peptides following a secondary cleavage within the prodomain. In this study, we used human embryonic kidney 293 (HEK293) cells to study the biosynthesis of rat or human PCSK4. Our results show that the bulk of PCSK4 remains as an intracellular zymogen, presumably trapped in the endoplasmic reticulum, where it interacts with the general molecular chaperone glucose-regulated protein 78/Immunoglobulin heavy-chain binding protein (GRP78/BiP). These data suggest that, unlike other members of the convertase family, proPCSK4 cannot efficiently self-activate in somatic cells. These cells may lack the intracellular environment and the interacting molecules specific to testicular germ cells where this enzyme is normally expressed.
人弗林蛋白酶前体加工内切蛋白酶的激活是通过分子内自蛋白水解裂解发生的。
DOI：
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发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Leduc,R;Molloy,SS;Thorne,BA;Thomas,G
通讯作者：
Thomas,G
影响因子：
11.4
作者：
MOLLOY, SS;THOMAS, L;THOMAS, G
通讯作者：
THOMAS, G