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Published on: August 27, 2013
CREB経由のタンパク質キナーゼAシグナル伝達は,Wntタンパク質によって誘発されたミオゲネシスを制御する
Alice E Chen1, David D Ginty, Chen-Ming Fan
1Department of Embryology, Carnegie Institution of Washington, 115 West University Parkway, Baltimore, Maryland 21210, USA.
Nature
|November 30, 2004
まとめ
Wntシグナリングは,タンパク質キナーゼA (PKA) とCREB.を介して,予期せぬ形で筋肉発達遺伝子を活性化させます. この経路は胚の筋肉形成に不可欠であり,幹細胞と癌に影響を与える可能性があります.
科学分野:
- 発達生物学 発達生物学とは
- 分子生物学は分子生物学である.
- 細胞シグナリング 細胞シグナリング
背景:
- Wntタンパク質は,胚の発達中にPax3,MyoD,Myf5のようなミオゲン遺伝子を誘発することが知られている.
- Wntシグナル伝達が,このミオゲン遺伝子発現を誘発する正確な分子機構は,ほとんど未定義のままである.
研究 の 目的:
- 菌原性決定性遺伝子のWnt誘発発現を媒介するシグナル伝達経路を解明する.
- タンパク質キナーゼA (PKA) とCREBがWnt誘導筋形成における役割を調査する.
主な方法:
- 遺伝子誘導を研究するために,インビトロエクスプラントアッセイが利用されました.
- 特定のシグナリングコンポーネントの必要性を評価するために,変異分析が行われました.
- エクスビボ培養マウス胚への遺伝子配送は,インビボ検証を許可した.
主要な成果:
- PKAの活性化につながるアデニリルサイクラゼシグナル伝達は,Wnt方向のミオゲン遺伝子発現に不可欠である.
- このプロセスには,PKAの標的である転写因子CREBが必要です.
- Wntタンパク質は,CREB媒介の転写を直接刺激することが示され,新しいWnt-PKA-CREB信号軸を示しています.
結論:
- CREB経由のタンパク質キナーゼA (PKA) シグナル伝達は,Wnt誘発の神経形成の重要な,以前に認識されていない媒介者です.
- この発見は,PKAとCREBを含む新しいWntシグナル伝達経路を明らかにしています.
- この発見は,PKA/CREBシグナル伝達が,Wnt調節された胚のパターニング,幹細胞の再生,がんの発症においてより広範な役割を果たす可能性があることを示唆している.
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02:54Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
01:41Non-Canonical Wnt Signaling Pathways
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