I

PKC-11

ERKs caspase apopt osis

Figure2. Overview of the role of the sphingomyelin cycle in apoptosis. A stress signal activates sphingomyelinase (SMase) which cleaves sphingomyelin (SM), forming ceramide. Ceramide can induce a ceramide-activated protein phosphatase (CAPP) and/or a ceramide-activated protein kinase (CAPK). CAPP effects can be blocked by Bcl-2 or PKC and leads to activation of caspases, and apoptosis. CAPK works through a different pathway, activating Raf-1 and then the extracellular signal regulated kinases (ERKs).

sphingomyelinase (a-SMase). Furthermore, the overexpression of Bcl-2, a known protector against apoptosis, has been able to protect cells from ceramide-induced apoptosis. Therefore, the study of sphingolipids in the process of apoptosis has become an important field.

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