The molecular mechanism of sphingosine kinase activation

许多细胞过程，如生长、死亡和分化，都是由激素和其他分子控制的，这些分子与细胞外部的受体相互作用。当这类分子与受体结合时，它通常会触发细胞内信号分子的产生，从而引发细胞行为的变化。脂质分子磷酸鞘氨醇已被确定为一种信号分子，似乎参与调节多种重要的哺乳动物细胞过程。最近的研究发现，磷酸鞘氨醇参与了细胞的炎症，如果它的产生可以被阻断，就看不到炎症。因此，这为炎症过程的治疗干预提供了一个潜在的靶点。然而，细胞调节鞘氨醇磷酸水平的方式尚不清楚。众所周知，磷酸鞘氨醇是由鞘氨醇激酶产生的，有力的证据表明，细胞中这种酶的活性变化调节了磷酸鞘氨醇的水平。然而，细胞如何改变鞘氨醇激酶活性的水平是完全未知的。这项研究将研究这个问题，并认为了解这一过程将允许开发新药来阻止鞘氨醇激酶活性的增加，防止鞘氨醇磷酸水平的增加，进而防止细胞炎症。

Many cell processes like growth, death and differentiation are controlled by hormones and other molecules that interact with receptors on the outside of the cell. When this type of molecule binds to a receptor, it often triggers the production of signaling molecules inside the cell that initiate a change in the cells behaviour. The lipid molecule, sphingosine phosphate has been identified as such a signaling molecule that appears to be involved in the regulation of a diverse array of important mammalian cellular processes. Recent studies have found that sphingosine phosphate is involved in the inflammation of cells, and if its production can be blocked, inflammation is not seen. Therefore, this provides a potential target for therapeutic intervention in the inflammation process. However, the manner by which cells regulate sphingosine phosphate levels is not well known. It is known that sphingosine phosphate is produced by the enzyme sphingosine kinase, and strong evidence suggests that changes in this enzyme's activity in the cell regulate sphingosine phosphate levels. However, how the cell changes the levels of sphingosine kinase activity is completely unknown. This study will investigate this problem with the view that understanding this process will allow the development of new drugs to block increases in sphingosine kinase activity, preventing increases in sphingosine phosphate levels, and it turn, preventing cellular inflammation.