Publication Date:
1992-03-27
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dressler, K A -- Mathias, S -- Kolesnick, R N -- 1 F32 GM14207-01/GM/NIGMS NIH HHS/ -- R0-1-CA-42385/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Mar 27;255(5052):1715-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1313189" target="_blank"〉PubMed〈/a〉
Keywords:
Cell-Free System
;
Ceramides/*physiology
;
Enzyme Activation
;
Humans
;
In Vitro Techniques
;
Phosphorylation
;
Protein Kinases/*metabolism
;
Receptor, Epidermal Growth Factor/metabolism
;
Receptors, Cell Surface/*physiology
;
Receptors, Tumor Necrosis Factor
;
Second Messenger Systems
;
Signal Transduction/*drug effects
;
Sphingomyelin Phosphodiesterase/*physiology
;
Sphingomyelins/*physiology
;
Tumor Cells, Cultured
;
Tumor Necrosis Factor-alpha/*pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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