Signal transduction through the sphingomyelin pathway Review uri icon


MeSH Major

  • Signal Transduction
  • Sphingomyelins


  • 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.

publication date

  • February 1994



  • Review



  • eng

Digital Object Identifier (DOI)

  • 10.1007/BF02815356

PubMed ID

  • 8086039

Additional Document Info

start page

  • 287

end page

  • 97


  • 21


  • 2-3