Publication Date:
1993-01-22
Description:
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-1 beta 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-1 beta 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-1 beta to stimulate IL-2 secretion. Thus, IL-1 beta signals through the sphingomyelin pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mathias, S -- Younes, A -- Kan, C C -- Orlow, I -- Joseph, C -- Kolesnick, R N -- R0-1-CA-42385/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):519-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Signal Transduction, 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/8424175" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Cell-Free System
;
Ceramides/*metabolism
;
Dose-Response Relationship, Drug
;
Interleukin-1/*pharmacology
;
Interleukin-2/biosynthesis
;
Kinetics
;
Mice
;
Molecular Sequence Data
;
Protein Kinases/metabolism
;
Signal Transduction/*drug effects
;
Sphingomyelin Phosphodiesterase/pharmacology
;
Sphingomyelins/*metabolism
;
Substrate Specificity
;
Thymoma
;
Thymus Neoplasms
;
Tumor Cells, Cultured
;
Type C Phospholipases/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
