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The molecular mechanism of sphingosine kinase activation

鞘氨醇激酶激活的分子机制

基本信息

批准号：
nhmrc : 232905
负责人：
Prof Stuart Pitson
金额：
$ 29.51万
依托单位：
依托单位国家：
澳大利亚
项目类别：
NHMRC Project Grants
财政年份：
2003
资助国家：
澳大利亚
起止时间：
2003-01-01 至 2005-12-31
项目状态：
已结题

来源：
https://researchdata.edu.au/molecular-mechanism-sphingosine-kinase-activation/100603
关键词：
molecular mechanism sphingosine kinase activation

项目摘要

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.

许多细胞过程，如生长，死亡和分化，都是由激素和其他与细胞外部受体相互作用的分子控制的。当这种类型的分子与受体结合时，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，鞘氨醇磷酸已被确定为这样的信号分子，似乎是在一系列重要的哺乳动物细胞过程的调节参与。最近的研究发现，磷酸鞘氨醇与细胞的炎症有关，如果能够阻断其产生，就不会出现炎症。因此，这为炎症过程中的治疗干预提供了潜在的靶标。然而，细胞调节磷酸鞘氨醇水平的方式并不清楚。已知磷酸鞘氨醇由鞘氨醇激酶产生，并且强有力的证据表明，细胞中这种酶的活性的变化调节磷酸鞘氨醇水平。然而，细胞如何改变鞘氨醇激酶活性水平是完全未知的。这项研究将调查这个问题，认为了解这个过程将允许开发新药来阻止鞘氨醇激酶活性的增加，防止磷酸鞘氨醇水平的增加，并反过来防止细胞炎症。