Tumor Necrosis Factor-α Activates the Sphingomyelin Signal Transduction Pathway in a Cell-Free System
SciencePublished 27 March 1992
K.A. Dressler, Shalini Mathias, Richard Kolesnick
Citations447
SJR quartileQ1
SJR score10.42
SNIP6.62
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TL;DR
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.
Abstract
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.
Keywords
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