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Mycではなく,Fosではなく,キナーゼ無活性Srccによって引き起こされるPDGFシグナルブロックの救済です
1Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Nature
|November 30, 1995
まとめ
血小板由来成長因子 (PDGF) は細胞の成長を刺激する. この研究は,Srcキナーゼが,PDGF誘発した線維芽細胞のDNA合成に不可欠なMyc活性化を制御することを明らかにしています.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- がん研究 がん研究
背景:
- PDGFのような成長因子は,線維芽細胞の増殖に不可欠な転写因子AP1とMycを含む早期の遺伝子を即座に活性化させます.
- Srcファミリーキナーゼは,PDGF誘発のDNA合成に不可欠である.
研究 の 目的:
- どの転写因子が,構成的に表現されると,支配的負のSrc.の抑制効果を克服できるかを調査する.
- 成長因子媒介による転写活性化におけるSrcキナーズの役割を明らかにする.
主な方法:
- 繊維芽細胞における支配的負の Src と Ras の発現.
- 転写因子Myc,Fos,Jun.の構成表現について
- DNA合成と遺伝子活性化の評価.
主要な成果:
- 構成的なMyc発現は,支配的-負のSrcによって誘発されたDNA合成ブロックを救出しました.
- 構成要素のFosとJunの表現は,支配的負のRasによって誘発されたブロックを救ったが,支配的負のSrcによって誘発されたブロックを救ったわけではない.
- これらの発見は,SrcキナーゼがMyc.の転写活性化を特異的に調節することを示しています.
結論:
- Srcキナーゼは,PDGFの下流のシグナル伝達経路において重要な役割を果たし,特にMyc転写因子の活性化を制御します.
- この経路を理解することは,成長因子媒介の細胞増殖を理解する上で極めて重要であり,がん研究にも影響を及ぼします.
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