Gααと関連したrap1GAPの同型によってERK/MAPK経路の活性化 (i)
N Mochizuki1, Y Ohba, E Kiyokawa
1Department of Pathology, Research Institute, International Medical Center of Japan, Tokyo.
Nature
|September 7, 1999
まとめ
G ((i) タンパク質のアルファサブユニットは,rap1GAPII.を募集することによってERK/MAPK経路を活性化します. これは,GTPに結合したRap1を減少させ,Ras-ERK/MAPKミトジェニック経路を活性化させます.
科学分野:
- 細胞の信号伝達経路は,
- 分子生物学は分子生物学である.
- Gタンパク質に結合した受容体.
背景:
- ヘテロトリメア型G ((i) タンパク質は,神経ペプチドおよびホルモン受容体のシグナル伝達に不可欠です.
- タンパク質サブユニット (アルファとベタガンマ) は,ERK/MAPKカスケードを活性化します.
- 構成的に活性なG ((alpha) i2 (gip2) は細胞を変容させ,未知のメカニズムでERK/MAPKを活性化します.
研究 の 目的:
- G(i) タンパク質アルファサブユニットがERK/MAPKカスケードを活性化するメカニズムを解明する.
- Ras-ERK/MAPK経路の新たなレギュレータを特定する.
- Rap1 GTPase活性化タンパク質II (rap1GAPII) がG(i) シグナル伝達における役割を調査する.
主な方法:
- タンパク質結合を評価するための共免疫プレシピテーション.
- 細胞転位検査は,タンパク質の局所化を監視するために行われます.
- GTPに結合したRap1アッセイで,Rap1の活性を定量化します.
- ERK/MAPKのアクティベーションアッセイ.
主要な成果:
- rap1GAPIIは,G ((i)) タンパク質のアルファサブユニットに特異的に結合する.
- G(i) 結合したm2-ムスカリニン受容体の刺激により,rap1GAPIIが膜に転位する.
- この転位は,GTPに結合したRap1レベルを低下させる.
- 減少したGTP結合Rap1は,ERK/MAPK経路を活性化します.
結論:
- G ((i) のアルファサブユニットは,Ras-ERK/MAPKミトジェニック経路を活性化します.
- この活性化は,rap1GAPIIの膜リクルートによって発生し,GTP結合Rap1.1を減少させます.
- rap1GAPIIは,G(i) アルファサブユニットとRas-ERK/MAPK経路の間の重要なリンクとして機能します.
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