The distal ectodomain of angiotensin-converting enzyme regulates its cleavage-secretion from the cell surface.
The distal ectodomain of angiotensin-converting enzyme regulates its cleavage-secretion from the cell surface.
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血管紧张素转换酶的远端胞外域调节其从细胞表面的裂解分泌。
DOI：
10.1073/pnas.95.1.138
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发表时间：
1998
影响因子：
11.1
通讯作者：
Sen,I
中科院分区：
文献类型：
--
作者：
Sadhukhan,R;Sen,GC;Ramchandran,R;Sen,I
血管紧张素转换酶（ACE）是一种被质膜结合的金属蛋白酶从细胞表面切割出来的I型外泌蛋白。然而，另一种I型外泌蛋白CD4不经历这种卵裂分泌。在这项研究中，我们研究了调节卵裂分泌过程的ACE蛋白的结构决定因素。替换和缺失突变表明，胞质结构域、跨膜结构域和包围ACE主要和次要切割位点的近膜区域不调节其切割。此外，含有CD4远端胞外结构域和ACE近膜、跨膜和细胞质结构域的嵌合蛋白，虽然被转运到细胞表面，但没有裂解分泌。相反，ACE的远端胞外结构域被证明是重要的决定因素：含有ACE的远端胞外结构域和CD4的近膜、跨膜和细胞质结构域的蛋白质被有效地从细胞表面切割出来。嵌合蛋白在CD4序列内被切割，相应的酶活性被化合物3（一种相对特异性的ACE分泌酶活性抑制剂）抑制。这些结果表明，在嵌合蛋白中，可切割蛋白（如ACE）的远端细胞外结构域可以在非切割蛋白（如CD4）的近膜结构域内诱导蛋白水解裂解。
Angiotensin-converting enzyme (ACE) is a type I ectoprotein that is cleaved off the cell surface by a plasma membrane-bound metalloprotease. However, CD4, another type I ectoprotein does not undergo such cleavage-secretion. In this study, we investigated the structural determinants of the ACE protein that regulate the cleavage-secretion process. Substitution and deletion mutations revealed that the cytoplasmic domain, the transmembrane domain, and the juxtamembrane region encompassing the major and the minor cleavage sites of ACE do not regulate its cleavage. Moreover, a chimeric protein containing the distal extracellular domain of CD4 and the juxtamembrane, transmembrane, and the cytoplasmic domains of ACE, although transported to the cell surface, was not cleavage-secreted. In contrast, the distal extracellular domain of ACE was shown to be the important determinant: a protein containing the distal extracellular domain of ACE and the juxtamembrane, transmembrane, and cytoplasmic domain of CD4 was efficiently cleaved off the cell surface. The chimeric protein was cleaved within the CD4 sequence and the responsible enzymatic activity was inhibited by Compound 3, a relatively specific inhibitor of the ACE secretase activity. These results demonstrate that, in a chimeric protein, the distal extracellular domain of a cleavable protein, such as ACE, can induce a proteolytic cleavage within the juxtamembrane domain of an uncleaved protein such as CD4.
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睾丸血管紧张素转换酶的两个特定残基的突变改变了其催化特性。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Sen,I;Kasturi,S;AbdulJabbar,M;Sen,GC
通讯作者：
Sen,GC
人促肿瘤坏死因子连接结构域的长度决定了切割加工。
影响因子：
2.9
作者：
Ping Tang;Mien Chie Hung;J. Klostergaard
通讯作者：
J. Klostergaard
DOI：
10.1016/s0021-9258(17)42144-2
发表时间：
1994-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Ramchandran;G. Sen;K. Misono;I. Sen
通讯作者：
R. Ramchandran;G. Sen;K. Misono;I. Sen
影响因子：
4.8
作者：
Ho, LB;Fukuchi, K;Younkin, SG
通讯作者：
Younkin, SG
在没有细胞质尾的情况下调节阿尔茨海默病β-淀粉样前体蛋白的裂解
影响因子：
3.3
作者：
O. D. C. E. Silva;K. Iverfeldt;T. Oltersdorf;S. Sinha;I. Lieberburg;T. V. Ramabhadran;T. Suzuki;S. Sisodia;S. Gandy;P. Greengard
通讯作者：
P. Greengard