γ-glutamyl leukotrienase, a γ-glutamyl transpeptidase gene family member, is expressed primarily in spleen

γ-glutamyl leukotrienase, a γ-glutamyl transpeptidase gene family member, is expressed primarily in spleen
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DOI:
10.1074/jbc.273.43.28277
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发表时间:
1998-10-23
影响因子:
4.8
通讯作者:
Lieberman, MW
Lieberman, MW
中科院分区:
生物学2区
文献类型:
--
作者:
Carter, BZ;Shi, ZZ;Lieberman, MW

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我们最近发现了一种称为γ-谷氨酰白三烯酶(GGL)的小鼠酶,可将白三烯C-4(LTC 4)转化为白三烯D-4(LTD 4)。它还切割一些其它谷胱甘肽(GSH)缀合物,但不切割GSH本身(Carter,B. Z.,Wiseman,A. L.,Orkiszewski河,巴拉德,K。D、欧,C.- N.,和Lieberman,M.W.(1997)J.Biol.Chem.272,12305-12310)。我们现在已经克隆了编码GGL活性的全长小鼠cDNA和相应的基因。GGL和γ-谷氨酰转肽酶构成一个小的基因家族。这两个cDNA共享57%的核苷酸同一性和41%的预测氨基酸序列同一性。它们的相应基因具有相似的内含子-外显子结构,并且相隔3个碱基。检索基因库和逆转录聚合酶链反应分析未能确定其他家庭成员。GGL转录起始位点的定位揭示了GGL启动子是TATA-少的,但含有启动子,转录起始的控制元件。GGL表达的北方印迹为阴性。通过核糖核酸酶保护、原位杂交和酶活性测定判断,脾脏GGL表达水平最高。GGL还在胸腺淋巴细胞、细支气管上皮细胞、肺间质细胞、肾近曲小管细胞和小肠以及大脑的隐窝细胞中表达。小脑和脑干神经元,但不是在神经胶质细胞。GGL在小鼠中广泛分布,表明这种酶的重要作用。
We have recently identified a mouse enzyme termed gamma-glutamyl leukotrienase (GGL) that converts leukotriene C-4 (LTC4) to leukotriene D-4 (LTD4). It also cleaves some other glutathione (GSH) conjugates, but not GSH itself (Carter, B. Z., Wiseman, A. L., Orkiszewski, R., Ballard, K. D., Ou, C.-N., and Lieberman, M.W. (1997) J. Biol. Chem. 272, 12305-12310). We have now cloned a full-length mouse cDNA coding for GGL activity and the corresponding gene. GGL and gamma-glutamyl transpeptidase constitute a small gene family. The two cDNAs share a 57% nucleotide identity and 41% predicted amino acid sequence identity. Their corresponding genes have a similar intron-exon organization and are located 3 kilobases apart. A search of Genbank and reverse transcription-polymerase chain reaction analysis failed to identify additional family members. Mapping of the GGL transcription start site revealed that the GGL promoter is TATA-less but contains an initiator, a control element for transcription initiation. Northern blots for GGL expression were negative. As judged by ribonuclease protection, in situ hybridization, and measurement of enzyme activity, spleen had the highest level of GGL expression. GGL is also expressed in thymic lymphocytes, bronchiolar epithelial cells, pulmonary interstitial cells, renal proximal convoluted tubular cells, and crypt cells of the small intestine as well as in cerebral. cerebellar, and brain stem neurons but not in glial cells. GGL is widely distributed in mice, suggesting an important role for this enzyme.