A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid
A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid
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DOI：
10.1074/jbc.m201659200
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发表时间：
2002-09-13
影响因子：
4.8
通讯作者：
Arai, H
中科院分区：
文献类型：
--
作者：
Sonoda, H;Aoki, J;Arai, H
溶血磷脂酸(LPA)是一种具有多种生物学特性的脂质介质，其合成途径尚未完全解决。我们报道了一种新的产生2-酰基-LPA的磷脂酶A(1)的克隆和性质。在GenBank(TM)数据库中，该基因被鉴定为磷脂酰丝氨酸(PS)特异的磷脂酰丝氨酸(PS-PILA(1))的同源物。当在昆虫Sf9细胞中表达时，该酶是从Triton X-100不溶部分回收的，对外源添加的磷脂底物没有任何催化活性。然而，从表达该酶的Sf9细胞获得的培养基能激活2-酰基-LPA的细胞受体EDG7/LPA(3)。当佛波酯或细菌磷脂酶D处理细胞时，EDG7的活性进一步增强，提示磷脂酶D参与了这一过程。在后一种情况下，质谱分析证实，LPA(1)水平增加，但其他溶血磷脂水平没有增加。该酶在人体几种组织中都有表达，如前列腺、睾丸、卵巢、胰腺，尤其是血小板。这些数据表明，该酶是一种膜相关的PA选择性聚乳酸(1)，并提示它在LPA的产生中具有作用。
Lysophosphatidic acid (LPA) is a lipid mediator with diverse biological properties, although its synthetic pathways have not been completely solved. We report the cloning and characterization of a novel phosphatidic acid (PA)-selective phospholipase A(1) (PLA(1)) that produces 2-acyl-LPA. The PLA(1) was identified in the GenBank(TM) data base as a close homologue of phosphatidylserine (PS)-specific PLA(1) (PS-PILA(1)). When expressed in insect Sf9 cells, this enzyme was recovered from the Triton X-100-insoluble fraction and did not show any catalytic activity toward exogenously added phospholipid substrates. However, culture medium obtained from Sf9 cells expressing the enzyme was found to activate EDG7/LPA(3), a cellular receptor for 2-acyl-LPA. The activation of EDG7 was further enhanced when the cells were treated with phorbol ester or a bacterial phospholipase D, suggesting involvement of phospholipase D in the process. In the latter condition, an increased level of LPA(1) but not other lysophospholipids, was confirmed by mass spectrometry analyses. Expression of the enzyme is observed in several human tissues such as prostate, testis, ovary, pancreas, and especially platelets. These data show that the enzyme is a membrane-associated PA-selective PLA(1) and suggest that it has a role in LPA production.