論文 - 詳細
| RRC ID | 1236 |
|---|---|
| 著者 | Yamauchi Y, Hayashi M, Abe-Dohmae S, Yokoyama S. |
| タイトル | Apolipoprotein A-I activates protein kinase C alpha signaling to phosphorylate and stabilize ATP binding cassette transporter A1 for the high density lipoprotein assembly. |
| ジャーナル | J Biol Chem |
| Abstract |
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. |
| 巻・号 | 278(48) |
| ページ | 47890-7 |
| 公開日 | 2003-11-28 |
| DOI | 10.1074/jbc.M306258200 |
| PII | S0021-9258(20)75818-7 |
| PMID | 12952980 |
| MeSH | ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters / metabolism* Apolipoprotein A-I / metabolism Apolipoprotein A-I / physiology* Apolipoproteins / metabolism Blotting, Western Calpain / antagonists & inhibitors Cell Line Diglycerides / metabolism Dose-Response Relationship, Drug Enzyme Activation Enzyme Inhibitors / pharmacology Fibroblasts / metabolism Green Fluorescent Proteins Humans Lipid Metabolism Lipoproteins, HDL / metabolism* Luminescent Proteins / metabolism Models, Biological Phosphorylation Protein Kinase C / antagonists & inhibitors Protein Kinase C / metabolism* Protein Kinase C-alpha RNA, Messenger / metabolism Recombinant Fusion Proteins / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Sphingomyelins / metabolism Time Factors Type C Phospholipases / antagonists & inhibitors |
| IF | 4.238 |
| 引用数 | 109 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | WI-38 |