文章基本信息

标题：Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase
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作者：Philipp Ternes ; Jos F. H. M. Brouwers ; Joep van den Dikkenberg 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2009
卷号：50
期号：11
页码：2270-2277
DOI：10.1194/jlr.M900230-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Sphingolipids are vital components of eukaryotic membranes involved in the regulation of cell growth, death, intracellular trafficking, and the barrier function of the plasma membrane (PM). While sphingomyelin (SM) is the major sphingolipid in mammals, previous studies indicate that mammalian cells also produce the SM analog ceramide phosphoethanolamine (CPE). Little is known about the biological role of CPE or the enzyme(s) responsible for CPE biosynthesis. SM production is mediated by the SM synthases SMS1 in the Golgi and SMS2 at the PM, while a closely related enzyme, SMSr, has an unknown biochemical function. We now demonstrate that SMS family members display striking differences in substrate specificity, with SMS1 and SMSr being monofunctional enzymes with SM and CPE synthase activity, respectively, and SMS2 acting as a bifunctional enzyme with both SM and CPE synthase activity. In agreement with the PM residency of SMS2, we show that both SM and CPE synthase activities are enhanced at the surface of SMS2-overexpressing HeLa cells. Our findings reveal an unexpected diversity in substrate specificity among SMS family members that should enable the design of specific inhibitors to target the biological role of each enzyme individually.
关键词：bifunctional enzyme ; sphingolipid biosynthesis ; ceramide homeostasis ; cell growth ; lipid asymmetry ; cervical carcinoma HeLa cells