Apolipoprotein A-I Activates Protein Kinase Cα Signaling to Phosphorylate and Stabilize ATP Binding Cassette Transporter A1 for the High Density Lipoprotein Assembly
Copyright policy )Apolipoprotein A-I Activates Protein Kinase Cα Signaling to Phosphorylate and Stabilize ATP Binding Cassette Transporter A1 for the High Density Lipoprotein Assembly
ATP-binding cassette transporter A1 (ABCA1) plays an essential role in the helical apolipoprotein-mediated assembly of high density lipoprotein, and the apolipoporteins stabilize ABCA1 against calpain-mediated degradation during the reaction ((2002) J. Biol. Chem. 277, 22426-22429). Protein kinase C (PKC) inhibitors suppressed both ABCA1 stabilization and cellular lipid release mediated by apolipoprotein A-I (apoA-I) but not ABCA1 increase by calpain inhibitors. The increase of ABCA1 and the cellular lipid release by apoA-I were both suppressed by a phosphatidylcholine phospholipase C (PC-PLC) inhibitor but not by the inhibitors of phosphatidylinositol-PLC and phosphatidylinositol 3-kinase. A protein phosphatase inhibitor further enhanced the ABCA1 increase by apoA-I. Biochemical and microscopic evidence indicated that apoA-I activated PKC alpha, and phosphorylation of ABCA1 was directly demonstrated by apoA-I via PKC. Finally, digestion of sphingomyelin increased ABCA1, and a PC-PLC inhibitor suppressed it. We conclude that apoA-I activates PKC alpha by PC-PLC-mediated generation of diacylglycerol initiated by the removal of cellular sphingomyelin ((2002) J. Biol. Chem. 277, 44709-44714), and subsequently phosphorylates and stabilizes ABCA1.
- Nagoya City University Japan
Apolipoprotein A-I, Dose-Response Relationship, Drug, Calpain, Blotting, Western, Green Fluorescent Proteins, Fibroblasts, Lipid Metabolism, Models, Biological, Cell Line, Diglycerides, Enzyme Activation, Luminescent Proteins, Apolipoproteins, Humans, ATP-Binding Cassette Transporters, Enzyme Inhibitors, Phosphorylation, Lipoproteins, HDL, Protein Kinase C, ATP Binding Cassette Transporter 1
Apolipoprotein A-I, Dose-Response Relationship, Drug, Calpain, Blotting, Western, Green Fluorescent Proteins, Fibroblasts, Lipid Metabolism, Models, Biological, Cell Line, Diglycerides, Enzyme Activation, Luminescent Proteins, Apolipoproteins, Humans, ATP-Binding Cassette Transporters, Enzyme Inhibitors, Phosphorylation, Lipoproteins, HDL, Protein Kinase C, ATP Binding Cassette Transporter 1
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