Sphingomyelin-ceramide turnover in CD28 costimulatory signaling.
When the CD28 membrane glycoprotein of T cells binds to its ligand, a signal is transmitted that is required for T cell receptor-induced proliferation and cytokine secretion: T cells are not stimulated by the CD28 signal alone. Ligation of CD28 initiated sphingomyelin hydrolysis and generated ceramide. Treatment of T cells with either exogenous sphingomyelinase or a cell-permeable ceramide analogue. C6-ceramide, mimicked the CD28 signal by inducing T cell proliferation and interleukin-2 gene transcription. Stabilization of interleukin-2 mRNA was also observed in C6-ceramide-treated cells. Thus, the sphingomyelin-ceramide pathway is a candidate for mediating the costimulatory signal.
Chan
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G
Autoimmunity Group, John P. Roberts Research Institute, London, Ontario, Canada.
Ochi
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A
D000818:Animals; D018106:CD28 Antigens / Q000502:physiology*; D002453:Cell Cycle; D002518:Ceramides / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D018106:CD28 Antigens; D002518:Ceramides; D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase; D013755:Tetradecanoylphorbol Acetate