SPHINGOSINE-1-PHOSPHATE AS 2ND MESSENGER IN CELL-PROLIFERATION INDUCED BY PDGF AND FCS MITOGENS
SPHINGOSINE-1-PHOSPHATE AS 2ND MESSENGER IN CELL-PROLIFERATION INDUCED BY PDGF AND FCS MITOGENS
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DOI：
10.1038/365557a0
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发表时间：
1993-10-07
期刊：
影响因子：
64.8
通讯作者：
SPIEGEL, S
中科院分区：
文献类型：
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作者：
OLIVERA, A;SPIEGEL, S
使用甘油磷脂代谢物作为第二信使的生长信号网络已被很好地表征1，2，但较少被称为鞘脂3，4，另一个主要类别的膜脂质衍生的第二信使。鞘脂代谢物鞘氨醇和鞘氨醇-1-磷酸盐通过一种不依赖于蛋白激酶C5，6的途径刺激静止的Swiss 3 T3成纤维细胞的生长，这一发现使鞘脂和细胞增殖之间出现了一种诱人的联系。鞘氨醇-1-磷酸是从鞘氨醇迅速产生，并可能介导其生物效应6。此外，鞘氨醇-1-磷酸触发钙动员6，7和磷脂酶D8激活的双重信号转导途径，这是控制细胞增殖的突出事件。在这里，我们报告，鞘氨醇激酶的激活和鞘氨醇-1-磷酸的形成是重要的信号转导途径激活的强效有丝分裂原血小板衍生生长因子（PDGF）和胎牛血清（FCS）。
GROWTH signalling networks that use glycerophospholipid metabolites as second messengers have been well characterized1,2, but less is known of the second messengers derived from sphingolipids3,4, another major class of membrane lipids. A tantalizing fink between sphingolipids and cellular proliferation has emerged from the discovery that the sphingolipid metabolites sphingosine and sphingosine-1-phosphate stimulate growth of quiescent Swiss 3T3 fibroblasts by a pathway that is independent of protein kinase C5,6. Sphingosine-1-phosphate is rapidly produced from sphingosine and may mediate its biological effects6. Furthermore, sphingosine-1-phosphate triggers the dual signal transduction pathways of calcium mobilization6,7 and activation of phospholipase D8, prominent events in the control of cellular proliferation. Here we report that activation of sphingosine kinase and the formation of sphingosine-1-phosphate are important in the signal transduction pathways activated by the potent mitogens platelet-derived growth factor (PDGF) and fetal calf serum (FCS).