THE SPHINGOMYELIN SIGNAL-TRANSDUCTION PATHWAY MEDIATES APOPTOSIS FOR TUMOR-NECROSIS-FACTOR, FAS, AND IONIZING-RADIATION

Recent evidence suggests that tumor necrosis factor alpha, Fas, and io nizing radiation employ the sphingomyelin pathway to trigger apoptosis . The sphingomyelin pathway is initiated by hydrolysis of plasma membr ane sphingomyelin to generate ceramide via a sphingomyelinase. Ceramid e serves as a second messenger stimulating a cascade of kinases and tr anscription factors that activate a final common pathway of programmed cell death. The extent to which this signaling system is used in apop tosis induced by other toxic modalities is not known, but accumulating evidence suggests that it is a commonly employed pathway that could b e exploited therapeutically.