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.
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