Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8
Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8
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DOI：
10.1046/j.1432-1327.2000.01617.x
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发表时间：
2000-10-01
期刊：
影响因子：
--
通讯作者：
Gorrell, MD
中科院分区：
文献类型：
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作者：
Abbott, CA;Yu, DMT;Gorrell, MD
二肽基肽酶（DPP）IV在T细胞共刺激、趋化因子生物学、II型糖尿病和肿瘤生物学中起作用。成纤维细胞活化蛋白（FAP）与肿瘤生长和肝硬化有关。在这里，我们描述了DPP 8，一种新的人类后脯氨酸二肽氨基肽酶，是同源的DPPIV和FAP。Northern-blot杂交结果显示，DPP 8 mRNA在组织中普遍表达，与DPPIV相似。DPP 8基因定位于染色体15 q22，与我们命名为DPP 9的19p13.3的密切相关基因不同。全长DPP 8 cDNA编码882个氨基酸的蛋白质，与DPPIV和FAP具有约27%的同一性和51%的相似性，但没有跨膜结构域，也没有N-连接或O-连接的糖基化。转染COS-7细胞的Western印迹和共聚焦显微镜显示DPP 8是在细胞质中表达的100 kDa单体蛋白。纯化的重组DPP 8水解DPPIV底物Ala-Pro、Arg-Pro和Gly-Pro。因此，重组DPP 8与DPPIV和FAP共享脯氨酸后二肽氨基肽酶活性。DPP 8酶活性具有中性pH最适值，这与其为非溶酶体相一致。DPP 8和DPPIV在组织表达模式和底物方面的相似性表明DPP 8在T细胞活化和免疫功能中的潜在作用。
Dipeptidyl peptidase (DPP) IV has roles in T-cell costimulation, chemokine biology, type-II diabetes and tumor biology. Fibroblast activation protein (FAP) has been implicated in tumor growth and cirrhosis. Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP. Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV. The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9. The full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation. Western blots and confocal microscopy of transfected COS-7 cells showed DPP8 to be a 100-kDa monomeric protein expressed in the cytoplasm. Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro. Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP. DPP8 enzyme activity had a neutral pH optimum consistent with it being nonlysosomal. The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.