Raf-1はMAPキナーゼ-キナーゼを活性化する
J M Kyriakis1, H App, X F Zhang
1Diabetes Unit, Medical Services, Massachusetts General Hospital, Charlestown 02129.
Nature
|July 30, 1992
まとめ
c-raf-1プロトオンコゲン産物であるセリン/スレオニンタンパク質キナーゼは,MAPキナーゼ-キナーゼ (MAPK-K) を直接活性化する. この発見は,MAPK-Kをc-Raf-1の最初の生理学的基板として特定し,細胞信号伝達経路の重要なステップを明確にします.
科学分野:
- 細胞生物学 細胞生物学
- 分子腫瘍学 分子腫瘍学
- シグナルトランスデュークション
背景:
- c-raf-1プロトオンコゲンは,細胞外刺激によって活性化されるセリン/スレオニンタンパク質キナーゼをコードする.
- 重要なシグナル伝達分子であるc-Raf-1の生理学的基底は,ほとんど不明のままである.
- ミトゲン活性化タンパク質 (MAP) キナーゼErk1とErk2は,MAPキナーゼ-キナーゼ (MAPK-K) によってリン酸化によって活性化されます.
研究 の 目的:
- c-Raf-1タンパク質キナーゼの生理学的基板を特定するために.
- MAPK-KとErk1/2.2の活性化におけるc-Raf-1の役割を調査する.
- 細胞シグナル伝達におけるMAPK-Kのアップストリームアクティベータを解明する.
主な方法:
- v-raf変換細胞における構成的に活性なMAPK-KとErk1/2の分析.
- 部分的に精製されたMAPK-Kとフォスファタゼ2A.を用いた酵素測定法.
- MAPK-Kの活性化を評価するために,精製されたc-Raf-1を用いたインビトロキナーゼアッセイ.
- MAPK-Kとc-Raf-1との相互作用を特徴付けるためのカチオン交換染色学.
主要な成果:
- MAPK-KとErk1/2は,v-raf変換細胞で構成的に活性であることが判明しました.
- フォスファタゼ2AはMAPK-Kを無効化したが,精製されたc-Raf-1はそれをin vitroで再活性化することができた.
- c-Raf-1は,MAPK-K.と共離する50,000M(r) ポリペプチドの選択的リン酸化を媒介した.
- これらの発見は,c-Raf-1がMAPK-K.の直接的な上流活性化剤であることを示しています.
結論:
- c-Raf-1は,MAPK-K.の直接的な上流活性化剤として特定されています.
- MAPK-Kは,c-raf-1プロトオンコゲン産物の生理学的基板として初めて特定されました.
- この研究は,c-Raf-1によって調節されるMAPキナーゼシグナリングカスケードの重要なステップを明らかにしています.
さらに関連する動画
07:49Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
06:44Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells
Published on: March 1, 2024
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