Phospholipid scramblase 3 is the mitochondrial target of protein kinase C delta-induced apoptosis.
Protein kinase C (PKC) delta translocates to mitochondria during apo-ptosis,but its mitochondrial target remains unclear. We found that PKC-delta physically interacted with and phosphorylated phospholipid scramblase 3 (PLS3) after UV irradiation. PLS3 is a high-affinity substrate for PKC-delta in vitro with the K(m) at 10.5 nM. Cells expressing wild-type PLS3 ... became apoptotic on phorbol ester stimulation, whereas the control cells did not. Expression of a mitochondrial-targeted PKC-delta enhanced apoptosis more prominently in HeLa-PLS3 cells than control HeLa cells and HeLa cells expressing an inactive PLS3 mutant. These results indicate that PLS3 is a downstream effector of PKC-delta in the mitochondria.
Mesh Terms:
Apoptosis, Carrier Proteins, Cloning, Molecular, Hela Cells, Humans, Kinetics, Membrane Proteins, Mitochondria, Phospholipid Transfer Proteins, Phosphorylation, Protein Kinase C, Protein Kinase C-delta, Tetradecanoylphorbol Acetate, Ultraviolet Rays
Apoptosis, Carrier Proteins, Cloning, Molecular, Hela Cells, Humans, Kinetics, Membrane Proteins, Mitochondria, Phospholipid Transfer Proteins, Phosphorylation, Protein Kinase C, Protein Kinase C-delta, Tetradecanoylphorbol Acetate, Ultraviolet Rays
Cancer Res.
Date: Mar. 15, 2003
PubMed ID: 12649167
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