Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5′-phosphate binding domain exposed to the cytosol

被引:121
作者
Ikeda, M [1 ]
Kihara, A [1 ]
Igarashi, Y [1 ]
机构
[1] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Biomembrane & Biofunct Chem, Kita Ku, Sapporo, Hokkaido 0600812, Japan
关键词
sphingosine-1-phosphate lyase; sphingosine-1-phosphate; sphingolipid; glycerophospholipid; endoplasmic reticulum; pyridoxal 5 '-phosphate; platelet;
D O I
10.1016/j.bbrc.2004.10.036
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:338 / 343
页数:6
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