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Updated: Aug 24, 2026
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Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
ミトゲン誘発のスレオニン/チロシンフォスファタゼPAC1によるMAPキナーゼ活性化の制御
1Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892.
Nature
|February 17, 1994
まとめ
PAC1は,ミトゲン活性化タンパク質 (MAP) キナーゼを不活性化するフォスファターゼです. この発見は,PAC1を明らかにしています.
科学分野:
- セルラー・シグナリング
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- ミトゲン刺激は,ミトゲン活性化タンパク質 (MAP) キナーゼERK1およびERK2.2を含む細胞内シグナリングカスケードを活性化させます.
- MAPキナーゼ活性化は,MAPキナーゼキナーゼ (MEK) による二重リン酸化によって発生する.
- 活性化されたMAPキナーゼは核に転位し,転写因子をリン酸化する.
研究 の 目的:
- MAPキナーゼの調節における,以前に特定された核チロシンフォスファタゼであるPAC1の役割を調査する.
- PAC1が生理学的に重要なMAPキナーゼ・フォスファタゼとして機能するかどうかを判断する.
主な方法:
- 再結合PAC1を二重特異性フォスファタゼとしてインビトロで特徴づける.
- MAPキナーゼに対するPAC1の基板特異性の評価.
- MAPキナーゼ活性への影響を評価するために,構成PAC1発現を含むインビボ試験.
- PAC1発現に続くMAPキナーゼ調節レポーター遺伝子発現の分析.
主要な成果:
- 再結合PAC1は,MAPキナーゼに対する高特異性を持つ二重特異性スレオニン/チロシンフォスファタゼ活性を示した.
- 構成的なPAC1発現は,表皮成長因子,ホルボルミリスチルアセテート,T細胞受容体クロスリンクによって刺激されたMAPキナーゼ活性を抑制した.
- PAC1媒介によるMAPキナーゼの不活性化は,MAPキナーゼ調節レポーター遺伝子発現の抑制につながった.
結論:
- PAC1は生理学的に重要なMAPキナーゼフォスファタゼである.
- PAC1は,MAPキナーゼシグナル伝達経路の調節に重要な役割を果たしています.
- MAPキナーゼのPAC1不活性化は,下流の転写調節に影響を与える.
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