タンパク質キナーゼCの活性化は,c-JunのDNA結合活性を否定的に調節する部位でのc-Junのリン酸化を低下させます
W J Boyle1, T Smeal, L H Defize
1Molecular Biology and Virology Laboratory, Salk Institute, La Jolla, California 92037.
Cell
|February 8, 1991
まとめ
休息している細胞では,c-Junタンパク質は,リン酸化によって不活性になります. タンパク質キナーゼCの活性化が脱リン酸化を誘発し,AP-1結合活性とc-Junを強化する.
科学分野:
- 分子生物学は分子生物学である.
- 細胞シグナリング
背景:
- c-Junは,遺伝子発現を調節する転写因子です.
- c-Junのリン酸化は,DNA結合およびトランス活性化活動に影響する.
研究 の 目的:
- c-Junのリン酸化が,その活性を調節する役割を調査する.
- 特定のリン酸化部位とそのDNA結合への影響を特定する.
主な方法:
- グリコーゲン合成キナーゼ3 (GSK-3) を使用したインビトロリン酸化アッセイ.
- c-Junのリン酸化部位のサイト指向型変異.
- タンパク質キナーゼCの活性化後のAP-1結合活動の分析.
主要な成果:
- GSK-3リン酸化物 c-Junは3つの特定の部位 (残留物227-252) で発見されました.
- タンパク質キナーゼCの活性化はc-Junの脱リン酸化を引き起こし,AP-1結合を増加させます.
- セリン243をフェニララニンに変異させると,c-Junのトランス活性化が10倍に増加する.
結論:
- c-Junは,静止細胞の潜在的,リン酸化状態で存在します.
- プロテインキナーゼCによって誘発されるサイト固有の脱リン酸化は,c-Jun.を活性化します.
- リン酸化状態は,c-Junの転写機能の重要な調節因子である.
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