構成的に活性なMAPキナーゼキナーゼによって哺乳類の細胞の変異
S J Mansour1, W T Matten, A S Hermann
1Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.
Science (New York, N.Y.)
|August 12, 1994
まとめ
構成的に活性なミトゲン活性化タンパク質キナーゼキナーゼ (MAPKK) 変異体は細胞変容を促進した. これらの発見は,MAPKKの活性化が腫瘍形成に十分であり,がん研究に影響を及ぼすことを示唆しています.
科学分野:
- 細胞生物学 細胞生物学
- 分子腫瘍学は分子腫瘍学である.
- 信号伝達経路は,信号の伝達経路である.
背景:
- ミトゲン活性化タンパク質 (MAP) キナーゼキナーゼ (MAPKK) は,成長および分化因子に対する細胞応答を調節する信号伝達経路において決定的な役割を果たします.
- ras, src, raf, mosなどの腫瘍遺伝子は,MAPKKの活性化を維持することによって細胞変異を引き起こすと仮定されています.
研究 の 目的:
- MAPKKの持続的な活性化が細胞変異を誘発するのに十分であるかどうかを調査する.
- 腫瘍性変異は,MAPKKと下流の信号構成要素の長期的活性化を伴うという仮説を検証する.
主な方法:
- 構成的に活性なMAPKK変異体で,基礎活性が著しく上昇した (400倍まで野生型より高い).
- これらの突然変異は哺乳類の細胞で発現した.
- AP-1-調節された転写,柔らかいアガーコロニー形成,ヌードマウスの腫瘍発生性を評価した.
主要な成果:
- 構成的に活性なMAPKK変異体の発現は,AP-1-調節された転写の活性化につながった.
- これらの変異体を発現する細胞は,変形した焦点形成を示した.
- これらの細胞は,軟アガーの効率的な成長と裸のマウスの高い腫瘍発生性を示した.
結論:
- MAPKKの構成的活性化は,細胞変容を促進するのに十分である.
- この研究は,MAPKKの過剰活性化と腫瘍発生を結びつける直接的な証拠を提供します.
- 発見は,がんの発症を理解し,治療目標の特定に意味を持つ.
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