Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase
Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase
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DOI：
10.1073/pnas.93.2.749
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发表时间：
1996-01-23
影响因子：
11.1
通讯作者：
Coyle, JT
中科院分区：
文献类型：
--
作者：
Carter, RE;Feldman, AR;Coyle, JT
本报告表明，被称为前列腺特异性膜抗原（PSM）的研究性前列腺癌标志物具有水解活性，具有N-乙酰化α-连接酸性二肽酶（NAALADase）的底物和药理学特性。NAALADase是一种膜水解酶，其在哺乳动物神经系统中的特征在于其催化神经肽N-乙酰基谷氨酸盐（NAAG）产生谷氨酸盐和N-乙酰基天冬氨酸盐，并被假设影响谷氨酸能信号传导过程，用抗NAALADase抗血清对大鼠脑cDNA表达文库进行免疫筛选，鉴定出一个1428碱基的部分cDNA，与对照组的86%同源。与人PSM cDNA的1428个碱基的序列同一性[Israeli，R.美国，鲍威尔，C。T.，很好，W。R，&赫斯顿，W. D. W.（1993）Cancer Res. 53，227-230]，随后通过逆转录-PCR从PSM阳性前列腺癌细胞系LNCaP中分离含有整个PSM开放阅读框架的cDNA。将该cDNA瞬时转染到两个NAALADase阴性细胞系中赋予NAAG水解活性，该活性被NAALADase抑制剂使君子酸和β-NAAG抑制，因此，我们证明了PSR编码的功能，并鉴定了NAALADase编码cDNA，北方分析鉴定了至少六种在NAALADase阳性但不在NAALADase阴性大鼠组织和人细胞系中表达的转录本;因此，PSM和/或相关分子种类似乎是神经系统中NAAG水解的原因，这些结果也提出了关于PSM在正常和病理前列腺上皮细胞功能中的作用的问题。
This report demonstrates that the investigational prostatic carcinoma marker known as the prostate-specific membrane antigen (PSM) possesses hydrolytic activity with the substrate and pharmacologic properties of the N-acetylated alpha-linked acidic dipeptidase (NAALADase). NAALADase is a membrane hydrolase that has been characterized in the mammalian nervous system on the basis of its catabolism of the neuropeptide N-acetylaspartylglutamate (NAAG) to yield glutamate and N-acetylaspartate and that has been hypothesized to influence glutamatergic signaling processes, The immunoscreening of a rat brain cDNA expression library with anti-NAALADase antisera identified a 1428-base partial cDNA that shares 86% sequence identity with 1428 bases of the human PSM cDNA [Israeli, R. S., Powell, C. T., Fair, W. R, & Heston, W. D. W. (1993) Cancer Res. 53, 227-230], A cDNA containing the entire PSM open reading frame was subsequently isolated by reverse transcription-PCR from the PSM-positive prostate carcinoma cell line LNCaP, Transient transfection of this cDNA into two NAALADase-negative cell lines conferred NAAG-hydrolyzing activity that was inhibited by the NAALADase inhibitors quisqualic acid and beta-NAAG, Thus we demonstrate a PSR-encoded function and identify a NAALADase-encoding cDNA, Northern analyses identify at least six transcripts that are variably expressed in NAALADase-positive but not in NAALADase-negative rat tissues and human cell lines; therefore, PSM and/or related molecular species appear to account for NAAG hydrolysis in the nervous system, These results also raise questions about the role of PSM in both normal and pathologic prostate epithelial-cell function.