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

被引：460

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

页码：1715 / 1718

页数：4

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