Regulation of Phospholipid Scramblase Activity during Apoptosis and Cell Activation by Protein Kinase CÎ

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...

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Veröffentlicht in:The Journal of biological chemistry 2000-07, Vol.275 (30), p.23065
Hauptverfasser: S. Courtney Frasch, Peter M. Henson, Jenai M. Kailey, Donald A. Richter, Michael S. Janes, Valerie A. Fadok, Donna L. Bratton
Format: Artikel
Sprache:eng
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Zusammenfassung: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) δ plays an important role in activated transbilayer movement of phospholipids and surface PS exposure by directly enhancing the activity of phospholipid scramblase. Specific inhibition of PKCδ by rottlerin prevented both apoptosis- and activation-induced scramblase activity. PKCδ 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 PKCδ and scramblase, but not scramblase or PKCδ alone in Chinese hamster ovary cells demonstrated enhanced scramblase activity.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M003116200