Molecular and Chemical Neuropathology

, Volume 21, Issue 2–3, pp 287–297

Signal transduction through the sphingomyelin pathway

  • Richard Kolesnick


The sphingomyelin pathway is a new signal transduction system initiated by hydrolysis of palsma 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)α, the ability of cell-permeable ceramide analogs to bypass receptor activation and mimic the effect of TNFα, and reconstitution of this cascade in a cell-free system, support the concept that the sphingomyelin pathway serves to signal TNFα-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.

Index Entries

Signal transduction sphingomyelin phorbol esters diacylglycerols ceramide kinase phospholipase C sphingosine epidermal growth factor receptor protein kinases 


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Copyright information

© Humana Press Inc. 1994

Authors and Affiliations

  • Richard Kolesnick
    • 1
  1. 1.The Laboratory of Signal TransductionMemorial Sloan-Kettering Cancer CenterNew York

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