The compartmentalization and translocation of the sphingosine kinases: mechanisms and functions in cell signaling and sphingolipid metabolism.
The compartmentalization and translocation of the sphingosine kinases: mechanisms and functions in cell signaling and sphingolipid metabolism.
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DOI：
10.3109/10409238.2011.580097
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发表时间：
2011-10
影响因子：
6.5
通讯作者：
Wattenberg B
中科院分区：
文献类型：
--
作者：
Siow D;Wattenberg B
鞘氨醇激酶（SK）脂质信号酶家族的成员，包括人类鞘氨醇激酶-1和-2 (SK1, SK2)，因其在许多生理和病理生理过程中的作用而受到相当多的关注。SKs被认为是基于它们产生有效的脂质第二信使鞘氨醇-1-磷酸的信号酶，鞘氨醇-1-磷酸是五个g蛋白连接受体家族的配体。SK1和-2都是细胞内酶，在其一级序列中不具有明显的膜锚结构域。天然底物（鞘氨醇和二氢鞘氨醇）是脂质，相应的产物也是脂质，因此可能倾向于与膜相关，这表明SKs的特定膜定位可能影响到底物的获取和产物的本地化生产。在这里，我们考虑鞘氨醇激酶作为酶定位到特定的细胞内位置，有时通过激动剂依赖的易位，靶向这些酶到这些位置的机制，以及这种定位的功能后果。不仅鞘磷脂激酶的信号输出受到亚细胞定位的影响，而且这些酶作为鞘脂代谢代谢调节因子的作用也可能受到影响。
Members of the sphingosine kinase (SK) family of lipid signaling enzymes, comprising sphingosine kinase-1 and -2 (SK1, SK2) in humans, are receiving considerable attention for their roles in a number of physiological and pathophysiological processes. The SKs are considered signaling enzymes based on their production of the potent lipid second messenger sphingosine-1-phosphate, which is the ligand for a family of five G-protein linked receptors. Both SK1 and -2 are intracellular enzymes and do not possess obvious membrane anchor domains within their primary sequences. The native substrates (sphingosine and dihydrosphingosine) are lipids, as are the corresponding products, and therefore would have a propensity to be membrane associated, suggesting that specific membrane localization of the SKs could affect both access to substrate and localized production of product. Here we consider the emerging picture of the sphingosine kinases as enzymes localized to specific intracellular sites, sometimes by agonist-dependent translocation, the mechanism targeting these enzymes to those sites, and the functional consequence of that localization. Not only is the signaling output of the sphingosine kinases affected by subcellular localization, but the role of these enzymes as metabolic regulators of sphingolipid metabolism may be impacted as well.
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DOI：
10.1126/science.1176709
发表时间：
2009-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hait NC;Allegood J;Maceyka M;Strub GM;Harikumar KB;Singh SK;Luo C;Marmorstein R;Kordula T;Milstien S;Spiegel S
通讯作者：
Spiegel S
影响因子：
4.8
作者：
Billich, A;Bornancin, F;Baumruker, T
通讯作者：
Baumruker, T
影响因子：
3.9
作者：
Hengst JA;Guilford JM;Fox TE;Wang X;Conroy EJ;Yun JK
通讯作者：
Yun JK
影响因子：
4.8
作者：
Gillies, Laura;Lee, Sue Chin;Pyne, Susan
通讯作者：
Pyne, Susan
影响因子：
4.8
作者：
Bu, Shizhong;Kapanadze, Bagrat;Trojanowska, Maria
通讯作者：
Trojanowska, Maria