Phosphatidate phosphohydrolase and signal transduction
Phosphatidate phosphohydrolase and signal transduction
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DOI：
10.1016/0009-3084(96)02545-5
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发表时间：
1996-05-24
影响因子：
3.4
通讯作者：
Waggoner, DW
中科院分区：
文献类型：
--
作者：
Brindley, DN;Waggoner, DW
在细胞的质膜上发现了一种不依赖于Mg2+、对n -乙基马来酰亚胺不敏感的磷酸酯磷酸水解酶（PAP-2），并对其进行了纯化。该酶是一种多功能磷酸水解酶，可以使磷酸酯、溶血磷酸酯、l-磷酸鞘氨醇和l-磷酸神经酰胺脱磷酸，这些底物是反应的竞争性抑制剂。PAP-2的作用可以终止这些生物活性脂质的信号传导，同时产生二酰基甘油、鞘氨醇和神经酰胺等化合物，这些化合物也是有效的信号分子。在磷脂代谢方面，鞘氨醇（或鞘氨醇-磷酸）刺激磷脂酶D，从而形成磷脂酸。同时，鞘氨醇抑制PAP-2活性，从而进一步增加磷酸盐浓度。相比之下，神经酰胺通过多种激动剂抑制磷脂酶D的激活，并增加磷脂酸、溶血磷脂酸、l-磷酸鞘氨酸和l-磷酸神经酰胺的去磷酸化。这些作用证明了甘油脂和鞘脂信号通路之间的“串扰”，以及PAP-2在细胞激活过程中参与调节这些通路产生的生物活性脂质的平衡。
A Mg2+-independent and N-ethylmaleimide-insensitive phosphatidate phosphohydrolase (PAP-2) has been identified in the plasma membrane of cells and it has been purified. The enzyme is a multi-functional phosphohydrolase that can dephosphorylate phosphatidate, lysophosphatidate, sphingosine l-phosphate and ceramide l-phosphate and these substrates are competitive inhibitors of the reaction. The action of PAP-2 could terminate signalling by these bioactive lipids and at the same time generates compounds such as diacylglycerol, sphingosine and ceramide which are also potent signalling molecules. In relation to phosphatidate metabolism, sphingosine (or sphingosine l-phosphate) stimulates phospholipase D and thus the formation of phosphatidate. At the same time sphingosine inhibits PAP-2 activity thus further increasing phosphatidate concentrations. By contrast, ceramides inhibit the activation of phospholipase D by a wide variety of agonists and increase the dephosphorylation of phosphatidate, lysophosphatidate, sphingosine l-phosphate and ceramide l-phosphate. These actions demonstrate 'cross-talk' between the glycerolipid and sphingolipid signalling pathways and the involvement of PAP-2 in modifying the balance of the bioactive lipids generated by these pathways during cell activation.