Activation of the sphingomyelin signaling pathway in intact EL4 cells and in a cell-free system by IL-1 beta.
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.
Mathias
S
S
Laboratory of Signal Transduction, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Younes
A
A
Kan
C C
CC
Orlow
I
I
Joseph
C
C
Kolesnick
R N
RN
D000595:Amino Acid Sequence; D000818:Animals; D002474:Cell-Free System; D002518:Ceramides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology; D013109:Sphingomyelins / Q000378:metabolism*; D013379:Substrate Specificity; D013945:Thymoma; D013953:Thymus Neoplasms; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000494:pharmacology
D002518:Ceramides; D007375:Interleukin-1; D007376:Interleukin-2; D013109:Sphingomyelins; D011494:Protein Kinases; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase