カセインキナーゼIIは,c-Jun DNA結合とAP-1活性に対する負の調節剤である
1Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla 92093-0636.
Cell
|September 4, 1992
まとめ
カセインキナーゼII (CKII) はc-Junをリン酸化し,DNA結合とAP-1活性を抑制する. この研究は,CKIIIIを明らかにしています.
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
- バイオケミストリー バイオケミストリー
背景:
- c-Junは,遺伝子発現を調節するAP-1転写因子の重要な成分です.
- c-Junのリン酸化は,そのDNA結合活動を抑制し,AP-1の転写機能に影響を与えます.
- c-ジュンリン酸化を司る特定のキナーゼとその調節的役割は完全に理解されていませんでした.
研究 の 目的:
- c-Jun.で,リン酸化阻害部位に起因するキナーゼを特定する.
- AP-1活性を調節するカゼインキナーゼII (CKII) の役割を明らかにする.
- CKII媒介によるc-Junのリン酸化がAP-1の転写機能にどのように影響するかを調査する.
主な方法:
- c-Junのリン酸化部位のサイト指向型変異.
- 純化されたカゼインキナーゼIIを用いたインビトロキナーゼアッセイ.
- ペプチドとCKIIを細胞に微量注入するインビヴォ研究.
- AP-1活動とc-Jun発現レベルの分析.
主要な成果:
- カセインキナーゼII (CKII) は,c-Jun.にThr-231とSer-249をリン酸化するキナーゼとして特定されました.
- セル-243をフェニララニンで代用すると,CKIIによるc-ジュンリン酸化が低下する.
- CKII阻害剤のマイクロインジェクションにより,AP-1活性とc-Jun発現が誘発された.
- CKIIのマイクロインジェクションは,ホルボールのエステルまたは抑制ペプチドによるAP-1誘導を抑制しました.
結論:
- カセインキナーゼII (CKII) は,c-Jun.をリン酸化することによってAP-1の活性を弱める上で重要な役割を果たします.
- CKIIは,AP-1の転写活動の負の調節剤として作用する.
- これらの発見は,細胞信号伝達経路におけるCKIIの新しい機能を明らかにしています.
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