Fig. 7. Schematic diagram of the role of GSK-3 in the signaling pathways of ceramide-induced mitochondrial apoptosis. During ceramide-induced apoptosis, activated PP2A induces GSK-3 dephosphorylation and activation indirectly through a PI 3-kinase-Akt-regulated pathway. How ceramide activates PP2A remains unknown. Also, how GSK-3 activates caspase-2 and caspase-8, which causes mitochondrial damage and apoptosis, needs to be deciphered. It is of particular interest to know whether there is cross-talk between GSK-3 and Bcl-2.