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.
Liu
Jihua
J
Huntsman Cancer Institute and Section of Oncology, Department of Medicine, University of Utah, Salt Lake City, Utah 84112, USA.
Chen
Jun
J
Dai
Qiang
Q
Lee
Ray M
RM
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014466:Ultraviolet Rays
D002352:Carrier Proteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate