Several novel protein kinase C (PKC) isozymes have been identified as substrates for caspase-3. We have previously shown that novel PKCε is cleaved during apoptosis in MCF-7 cells that lack any functional caspase-3. In the present study, we show that in vitro-translated PKCε is processed by human recombinant caspase-3, -7, and -9. Tumor necrosis factor-α (TNF) triggered processing of PKCε to a 43-kDa carboxyl-terminal fragment, and cell-permeable caspase inhibitors prevented TNF-induced processing of PKCε in MCF-7 cells. PKCε was cleaved primarily at the SSPD ↓ G site to generate two fragments with an approximate molecular mass of 43 kDa. It was also cleaved at the DDVD ↓ C site to generate two fragments with molecular masses of 52 and 35 kDa. Treatment of MCF-7 cells with TNF resulted in the activation of PKCε, and mutation at the SSPD ↓ G (D383A) site inhibited proteolytic activation of PKCε. Over-expression of wild-type but not dominant-negative PKCε in MCF-7 cells delayed TNF-induced apoptosis, and mutation at the D383A site prevented antiapoptotic activity of PKCε. These results suggest that cleavage of PKCε by caspase-7 at the SSPD ↓ G site results in the activation of PKCε. Furthermore, activation of PKCε was associated with its antiapoptotic function.
CITATION STYLE
Basu, A., Lu, D., Sun, B., Moor, A. N., Akkaraju, G. R., & Huang, J. (2002). Proteolytic activation of protein kinase C-ε by caspase-mediated processing and transduction of antiapoptotic signals. Journal of Biological Chemistry, 277(44), 41850–41856. https://doi.org/10.1074/jbc.M205997200
Mendeley helps you to discover research relevant for your work.