Activation of the sphingomyelin signaling pathway in intact EL4 cells and in a cell-free system by IL-1β Journal Article


Authors: Mathias, S.; Younes, A.; Kan, C. C.; Orlow, I.; Joseph, C.; Kolesnick, R. N.
Article Title: Activation of the sphingomyelin signaling pathway in intact EL4 cells and in a cell-free system by IL-1β
Abstract: The mechanism of interleukin-1 (IL-1) signaling is unknown. Tumor necrosis factor-α 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-1β 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-1β 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-1β to stimulate IL-2 secretion. Thus, IL-1β signals through the sphingomyelin pathway.
Keywords: signal transduction; nonhuman; animal cell; mouse; animal; mice; protein kinases; interleukin 1beta; dose-response relationship, drug; tumor cells, cultured; amino acid sequence; molecular sequence data; tumor necrosis factor alpha; kinetics; substrate specificity; thymoma; thymus neoplasms; interleukin-2; ceramide; ceramides; sphingomyelin phosphodiesterase; interleukin-1; sphingomyelin; cell-free system; sphingomyelins; phospholipase c; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: Science
Volume: 259
Issue: 5094
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 1993-01-22
Start Page: 519
End Page: 522
Language: English
DOI: 10.1126/science.8424175
PUBMED: 8424175
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
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MSK Authors
  1. Irene Orlow
    247 Orlow
  2. Richard N Kolesnick
    299 Kolesnick
  3. Chu-Cheng Kan
    8 Kan
  4. Anas Younes
    320 Younes