NF-IL6/LAPによるトランザクティベーションは,その活性化ドメインのリン酸化によって強化されます
C Trautwein1, C Caelles, P van der Geer
1Department of Medicine, University of California, San Diego.
Nature
|August 5, 1993
まとめ
核因子IL6/肝臓関連タンパク質 (NF-IL6/LAP) は急性相応答を調節する. タンパク質キナーゼC経路の刺激は,Ser 105のリン酸化を介してNF-IL6/LAPの転写効果を高めます.
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
- 遺伝子規制 遺伝子規制
背景:
- NF-IL6/LAP (C/EBP beta) は,肝核における急性相応答に不可欠なbZIP転写因子である.
- IL-6,IL-1,リポポリサッカリドなどの炎症媒介物質によって誘発され,IL-6プロモーターの活性を調節する.
- NF-IL6/LAPの発現と活動を制御する正確な制御メカニズムは,まだ完全に理解されていません.
研究 の 目的:
- NF-IL6/LAP活動を調節するシグナル伝達経路の解明.
- NF-IL6/LAP機能を調節するタンパク質キナーゼC (PKC) の役割を調査する.
- NF-IL6/LAPの転写活動に影響を与える特定のリン酸化部位を特定する.
主な方法:
- NF-IL6/LAPの活性を調べるために,細胞ベースのアッセイを使用しました.
- 特定のアクティベータを使用したタンパク質キナーゼC経路を刺激する.
- セル105リン酸化の役割を調査するために,サイト指向型変異を生成した.
- NF-IL6/LAP標的遺伝子の転写活性化を評価した.
主要な成果:
- タンパク質キナーゼC経路の刺激により,セル105.5でNF-IL6/LAPのリン酸化が増加することが示されました.
- アクティベーションドメイン内のSer 105のリン酸化がNF-IL6 / LAPの転写有効性を高めることを示しました.
- NF-IL6/LAP活動の新たな規制メカニズムを特定しました.
結論:
- タンパク質キナーゼC媒介によるセル105のリン酸化は,NF-IL6/LAPの転写活性を増やすための重要なメカニズムです.
- この発見は,急性期応答の複雑な調節に関する新しい洞察を提供します.
- この信号伝達経路に関するさらなる研究は,炎症性疾患の治療標的を明らかにする可能性がある.
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