TUMOR-NECROSIS-FACTOR-ALPHA ACTIVATES THE SPHINGOMYELIN SIGNAL TRANSDUCTION PATHWAY IN A CELL-FREE SYSTEM

被引：456
|
作者：
DRESSLER, KA [1 ]
MATHIAS, S [1 ]
KOLESNICK, RN [1 ]
机构：
[1] MEM SLOAN KETTERING CANC CTR,SLOAN KETTERING INST,SIGNAL TRANSDUCT LAB,NEW YORK,NY 10021
来源：
SCIENCE | 1992年 / 255卷 / 5052期
关键词：
D O I：
10.1126/science.1313189
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The mechanism of tumor necrosis factor (TNF)-alpha signaling is unknown. TNF-alpha-signaling may involve sphingomyelin hydrolysis to ceramide by a sphingomyelinase and stimulation of a ceramide-activated protein kinase. In a cell-free system, TNF-alpha-induced a rapid reduction in membrane sphingomyelin content and a quantitative elevation in ceramide concentrations. Ceramide-activated protein kinase activity also increased. Kinase activation was mimicked by addition of sphingomyelinase but not by phospholipases A2, C, or D. Reconstitution of this cascade in a cell-free system demonstrates tight coupling to the receptor, suggesting this is a signal transduction pathway for TNF-alpha.
引用
收藏
页码：1715 / 1718
页数：4
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