Cloning and characterization of CPVL, a novel serine carboxypeptidase, from human macrophages
Cloning and characterization of CPVL, a novel serine carboxypeptidase, from human macrophages
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DOI：
10.1006/geno.2000.6484
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发表时间：
2001-03-15
期刊：
影响因子：
4.4
通讯作者：
McKnight, AJ
中科院分区：
文献类型：
--
作者：
Mahoney, JA;Ntolosi, B;McKnight, AJ
羧肽酶是从蛋白质或肽的羧基末端切割单个氨基酸的蛋白酶。除了在肠道中的降解功能之外，羧肽酶还活化或降解生物活性肽，如血管紧张素、缓激肽和内皮素I。利用差异显示PCR技术，我们克隆了一种在人巨噬细胞中表达而在其它白细胞中不表达的新的羧肽酶。该基因产物由476个氨基酸组成，具有一个假定的信号序列，但没有跨膜结构域，与真核生物中的丝氨酸羧肽酶家族有惊人的序列相似性。在已知的蛋白质中，该基因与卵黄生成羧肽酶（一种在蚊子卵巢中表达的丝氨酸羧肽酶）最相似（43%氨基酸同一性）。因此，我们将这种新基因命名为羧肽酶，卵黄生成样（CPVL）。除了单核细胞/巨噬细胞丰富的来源，如脾，白细胞和胎盘，CPVL mRNA在心脏和肾脏中大量表达，表明CPVL在免疫系统外的单独作用。CPVL基因在人染色体7 p14-p15上含有至少13个外显子，分布在超过150 kb的区域。亲和纯化的多克隆抗血清识别巨噬细胞裂解物中的约57 kDa的蛋白，但不识别来自淋巴细胞、中性粒细胞或单核细胞的裂解物中的蛋白。在单核细胞成熟为巨噬细胞期间诱导CPVL蛋白表达，CPVL在巨噬细胞中的可能功能包括消化溶酶体中的吞噬颗粒，参与炎性蛋白酶级联反应，以及修剪抗原呈递肽。(C)北京：科学出版社.
Carboxypeptidases are proteases that cleave single amino acids from the carboxy termini of proteins or peptides, Tn addition to degradative functions in the gut, carboxypeptidases activate or inactivate bioactive peptides such as angiotensin, bradykinin, and endothelin I. Using differential display PCR, we cloned a novel carboxypeptidase expressed in human macrophages but not in other leukocytes, The 476-amino-acid gene product has a putative signal sequence but no transmembrane domain and has striking sequence similarity to serine carboxypeptidases, a large family of enzymes in eukaryotes, Only one serine carboxypeptidase, lysosomal protective protein, has previously been reported in mammals. Among known proteins, this gene is most similar (43% amino acid identity) to vitellogenic carboxypeptidase, a serine carboxypeptidase expressed in mosquito ovaries. Therefore, we have named this new gene carboxypeptidase, vitellogenic-like (CPVL), In addition to monocyte/macrophage-rich sources such as spleen, leukocytes, and placenta, CPVL mRNA is abundantly expressed in heart and kidney, suggesting a separate role for CPVL outside the immune system. The CPVL gene contains at least 13 exons spread over more than 150 kb on human chromosome 7p14-p15, An affinity-purified polyclonal antiserum recognized a protein of approximately 57 kDa in macrophage lysates, but not in lysates from lymphocytes, neutrophils, or monocytes, CPVL protein expression was induced during maturation of monocytes into macrophages, Possible functions for CPVL in macrophages include digestion of phagocytosed particles in the lysosome, participation in an inflammatory protease cascade, and trimming of peptides for antigen presentation. (C) 2001 Academic Press.