Signal transduction through the sphingomyelin pathway.
The sphingomyelin pathway is a new signal transduction system initiated by hydrolysis of plasma membrane sphingomyelin to ceramide by the actin of a neutral sphingomyelinase. Ceramide serine/threonine protein kinase termed ceramide-activated protein kinase. This kinase belongs to a family of proline-directed protein kinases that recognize substrates containing the minimal motif, X-Thr/Ser-Pro-X, where the phosphoacceptor site is followed on the carboxyl terminus by a proline residue and X may be any amino acid. Three lines of evidence, rapid kinetics of activation of the sphingomyelin pathway by tumor necrosis factor (TNF) alpha, the ability of cell-permeable ceramide analogs to bypass receptor activation and mimic the effect of TNF alpha, and reconstitution of this cascade in a cell-free system, support the concept that the sphingomyelin pathway serves to signal TNF alpha-induced monocytic differentiation. Hence, the sphingomyelin pathway may represent a signaling system analogous to more well-defined systems such as the cyclic adenosine monophosphate and phosphoinositide pathways.
Kolesnick
R
R
Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000502:physiology*; D013379:Substrate Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
D013109:Sphingomyelins; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D013108:Sphingomyelin Phosphodiesterase