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GSK-3β acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 in ceramide-induced mitochondrial apoptosis.
- Source :
- Journal of Cell Science; 8/15/2007, Vol. 120 Issue 16, p18-18, 1p
- Publication Year :
- 2007
-
Abstract
- The signaling of glycogen synthase kinase-3β (GSK-3β) has been implicated in stress-induced apoptosis. However, the pro-apoptotic role of GSK-3β is still unclear. Here, we show the involvement of GSK-3β in ceramide-induced mitochondrial apoptosis. Ceramide induced GSK-3β activation via protein dephosphorylation at serine 9. We previously reported that ceramide induced caspase-2 and caspase-8 activation, Bid cleavage, mitochondrial damage, and apoptosis. In this study, we found that caspase-2 activation and the subsequent apoptotic events were abolished by the GSK-3β inhibitors lithium chloride and SB216763, and by GSK-3β knockdown using short interfering RNA. We also found that ceramide-activated protein phosphatase 2A (PP2A) indirectly caused GSK-3β activation, and that the PP2A-regulated PI 3-kinase-Akt pathway was involved in GSK-3β activation. These results indicate a role for GSK-3β in ceramide-induced apoptosis, in which GSK-3β acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 and caspase-8. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219533
- Volume :
- 120
- Issue :
- 16
- Database :
- Complementary Index
- Journal :
- Journal of Cell Science
- Publication Type :
- Academic Journal
- Accession number :
- 26364832
- Full Text :
- https://doi.org/10.1242/jcs.03473