Regulation of phospholipid scramblase activity during apoptosis and cell activation by protein kinase Cδ

Phospholipid scramblase induces nonspecific bidirectional movement of phospholipids across the membrane during cell activation and has been proposed to mediate the appearance of phosphatidylserine (PS) in the plasma membrane outer leaflet during apoptosis, a cell surface change that is critical for apoptotic cell removal. We report here that protein kinase C (PKC) delta plays an important role in activated transbilayer movement of phospholipids and surface PS exposure by directly enhancing the activity of phospholipid scrambIase, Specific inhibition of PKC delta by rottlerin prevented both apoptosis- and activation-induced scrambIase activity. PKC delta was either selectively cleaved and activated in a caspase 3-dependent manner (during apoptosis) or translocated to the plasma membrane (in stimulated cells) and could directly phosphorylate scramblase immunoprecipitated from Jurkat cells. Furthermore, reconstitution of PKC delta and scramblase, but not scramblase or PKC delta alone in Chinese hamster ovary cells demonstrated enhanced scramblase activity.