Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5′-phosphate binding domain exposed to the cytosol
Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5′-phosphate binding domain exposed to the cytosol
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DOI：
10.1016/j.bbrc.2004.10.036
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发表时间：
2004-12-03
影响因子：
3.1
通讯作者：
Igarashi, Y
中科院分区：
文献类型：
--
作者：
Ikeda, M;Kihara, A;Igarashi, Y
鞘氨醇-1-磷酸(S1P)是一种鞘糖脂代谢物，具有生物活性脂质分子的功能。S1P被S1P裂解酶或S1P磷酸水解酶降解。哺乳动物S1P裂解酶基因SPL已被鉴定。在这里，我们描述了SPL蛋白的表达、定位和拓扑结构。在大多数组织中，SPL蛋白的表达水平与二氢鞘氨醇-1-磷酸裂解酶(DHS1P)的活性有很好的相关性。然而，肝脏和心脏的DHS1P裂解酶活性高于它们的SPL蛋白水平。在小鼠胚胎发育过程中，SPL基因的表达受时间调控。免疫荧光显微镜显示SPL定位于内质网。酶K消化研究表明，含有活性部位的大亲水结构域面向胞浆。这一活性部位的方向与S1P磷酸水解酶相反，表明两种S1P降解酶对S1P的降解发生在内质网空间分离的一侧。(C)2004 Elsevier Inc.保留所有权利。
Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that functions as a bioactive lipid molecule. S1P is degraded either by S1P lyase or by S1P phosphohydrolase. The gene encoding mammalian S1P lyase, SPL, has been identified. Here, we characterize the SPL protein in its expression, localization, and topology. The expression levels of the SPL protein correlated well with the dihydrosphingosine- 1-phosphate (DHS1P) lyase activity in most tissues. However, liver and heart exhibited high DHS1P lyase activities compared to their SPL protein levels. The SPL mRNA expression was temporally regulated during mouse embryonal development. Immunofluorescence microscopy demonstrated that SPL is localized at the endoplasmic reticulum. Proteinase K digestion studies revealed that the large hydrophilic domain, containing the active site, faces the cytosol. This active site orientation is opposite to that of S1P phosphohydrolase, indicating that the degradation of S1P by two S1P-degrading enzymes occurs in spatially separated sides of the endoplasmic reticulum. (C) 2004 Elsevier Inc. All rights reserved.