The role of sphingomyelin cycle metabolites in transduction of signals of cell proliferation, differentiation and death.

Sphingomyelin cycle metabolites ceramide, sphingosine and sphingosine 1-phosphate play an important role in cell proliferation, differentiation, reception, oncogenesis and apoptosis. Ceramide is an intracellular second messenger for apoptosis activating proteases and specific phosphatases. Sphingosine is an endogenous inhibitor of protein kinase C and has an inhibitory effect on many cell functions depending on the activity of this enzyme. On the other hand, sphingosine can activate other kinases depending on the concentration, cell type and nature of a stimulus and release Ca2+ from intracellular stores thereby regulating cell proliferation. Sphingosine induces apoptosis and its level is increased in cells as a result of action of apoptotic inducers. A phosphorylated product of sphingosine, sphingosine 1-phosphate, mediates the mitogenic signal, induces Ca2+ mobilization and protects cells from apoptosis resulting from elevation of ceramide. The quantitative levels of sphingomyelin metabolites in the cell determine the dynamic balance between the apoptotic and mitogenic signals.