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TY - JOUR AU - Verheij, Marcel AU - Bose, Ron AU - Hua Lin, Xin AU - Yao, Bei AU - Jarvis, W. David AU - Grant, Steven AU - Birrer, Michael J. AU - Szabo, Eva AU - Zon, Leonard I. AU - Kyriakis, John M. AU - Haimovitz-Friedman, Adriana AU - Fuks, Zvi AU - Kolesnick, Richard N. PY - 1996 DA - 1996/03/01 TI - Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis JO - Nature SP - 75 EP - 79 VL - 380 IS - 6569 AB - THE induction of programmed cell death, or apoptosis, involves activation of a signalling system, many elements of which remain unknown1. The sphingomyelin pathway, initiated by hydrolysis of the phospholipid sphingomyelin in the cell membrane to generate the second messenger ceramide2,3, is thought to mediate apoptosis in response to tumour-necrosis factor (TNF)-α2,3, to Fas ligand4 and to X-rays5. It is not known whether it plays a role in the stimulation of other forms of stress-induced apoptosis. Given that environmental stresses also stimulate a stress-activated protein kinase (SAPK/JNK) 6–12, the sphingomyelin and SAPK/ JNK signalling systems may be coordinated in induction of apoptosis. Here we report that ceramide initiates apoptosis through the SAPK cascade and provide evidence for a signalling mechanism that integrates cytokine- and stress-activated apoptosis. SN - 1476-4687 UR - https://doi.org/10.1038/380075a0 DO - 10.1038/380075a0 ID - Verheij1996 ER -