Sphingosine-1-phosphate in cell growth and cell death

Ann N Y Acad Sci. 1998 Jun 19;845:11-8. doi: 10.1111/j.1749-6632.1998.tb09658.x.


Recent evidence suggests that branching pathways of sphingolipid metabolism may mediate either apoptotic or mitogenic responses depending on the cell type and the nature of the stimulus. While ceramide has been shown to be an important regulatory component of apoptosis induced by tumor necrosis factor alpha and Fas ligand, sphingosine-1-phosphate (SPP), a further metabolite of ceramide, has been implicated as a second messenger in cellular proliferation and survival induced by platelet-derived growth factor, nerve growth factor, and serum. SPP protects cells from apoptosis resulting from elevations of ceramide. Inflammatory cytokines stimulate sphingomyelinase, but not ceramidase, leading to accumulation of ceramide, whereas growth signals also leading to accumulation of ceramide, whereas growth signals also stimulate ceramidase and sphingosine kinase leading to increased SPP levels. We propose that the dynamic balance between levels of sphingolipid metabolites, ceramide, and SPP, and consequent regulation of different family members of mitogen-activated protein kinases (JNK versus ERK), is an important factor that determines whether a cell survives or dies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Division / physiology*
  • Ceramides / pharmacology
  • Ceramides / physiology
  • Humans
  • Lysophospholipids*
  • Nerve Growth Factors / pharmacology
  • Receptors, Cell Surface / physiology
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophospholipid
  • Signal Transduction*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology
  • fas Receptor / physiology


  • Ceramides
  • Lysophospholipids
  • Nerve Growth Factors
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • sphingosine 1-phosphate
  • Sphingosine