Delon Christine, Manifava Maria, Wood Eleanor, Thompson Dawn, Krugmann Sonja, Pyne Susan, Ktistakis Nicholas T
Department of Signalling, Babraham Institute, Cambridge CB2 4AT, United Kingdom.
J Biol Chem. 2004 Oct 22;279(43):44763-74. doi: 10.1074/jbc.M405771200. Epub 2004 Aug 13.
Sphingosine kinase 1 (SK1) phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). Because both substrate and product of the enzyme are potentially important signaling molecules, the regulation of SK1 is of considerable interest. We report that SK1, which is ordinarily a cytosolic enzyme, translocates in vivo and in vitro to membrane compartments enriched in phosphatidic acid (PA), the lipid product of phospholipase D. This translocation depends on direct interaction of SK1 with PA, because recombinant purified enzyme shows strong affinity for pure PA coupled to Affi-Gel. The SK1-PA interaction maps to the C terminus of SK1 and is independent of catalytic activity or of the diacylglycerol kinase-like domain of the enzyme. Thus SK1 constitutes a novel, physiologically relevant PA effector.
鞘氨醇激酶1（SK1）将鞘氨醇磷酸化生成1-磷酸鞘氨醇（S1P）。由于该酶的底物和产物都是潜在的重要信号分子，因此SK1的调节备受关注。我们报告称，SK1通常是一种胞质酶，在体内和体外均可转位至富含磷脂酸（PA）的膜区室，PA是磷脂酶D的脂质产物。这种转位依赖于SK1与PA的直接相互作用，因为重组纯化的酶对偶联到Affi-Gel上的纯PA表现出很强的亲和力。SK1与PA的相互作用定位于SK1的C末端，且与酶的催化活性或二酰基甘油激酶样结构域无关。因此，SK1构成了一种新型的、具有生理相关性的PA效应器。
