ACTIVATION OF THE SPHINGOMYELIN SIGNALING PATHWAY IN INTACT EL4 CELLS AND IN A CELL-FREE SYSTEM BY IL-1-BETA
ACTIVATION OF THE SPHINGOMYELIN SIGNALING PATHWAY IN INTACT EL4 CELLS AND IN A CELL-FREE SYSTEM BY IL-1-BETA
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DOI：
10.1126/science.8424175
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发表时间：
1993-01-22
期刊：
影响因子：
56.9
通讯作者：
KOLESNICK, RN
中科院分区：
文献类型：
--
作者：
MATHIAS, S;YOUNES, A;KOLESNICK, RN
白细胞介素-1 (IL-1) 信号传导的机制尚不清楚。肿瘤坏死因子-α 使用涉及鞘磷脂水解为神经酰胺和刺激神经酰胺激活蛋白激酶的信号转导途径。在完整的 EL4 胸腺瘤细胞中，IL-1β 类似地刺激鞘磷脂快速减少和神经酰胺升高，并增强神经酰胺激活蛋白激酶活性。在无细胞系统中，该级联也被 IL-1beta 激活，证明与受体紧密耦合。外源性鞘磷脂酶（但不是磷脂酶 A2、C 或 D）与佛波酯联合取代 IL-1β 以刺激 IL-2 分泌。因此，IL-1β 通过鞘磷脂途径发出信号。
The mechanism of interleukin-1 (IL-1) signaling is unknown. Tumor necrosis factor-alpha uses a signal transduction pathway that involves sphingomyelin hydrolysis to ceramide and stimulation of a ceramide-activated protein kinase. In intact EL4 thymoma cells, IL-1beta similarly stimulated a rapid decrease of sphingomyelin and an elevation of ceramide, and enhanced ceramide-activated protein kinase activity. This cascade was also activated by IL-1beta in a cell-free system, demonstrating tight coupling to the receptor. Exogenous sphingomyelinase, but not phospholipases A2, C, or D, in combination with phorbol ester replaced IL-1beta to stimulate IL-2 secretion. Thus, IL-1beta signals through the sphingomyelin pathway.