タンパク質マイクロアレイを用いたErbB受容体の定量タンパク質相互作用ネットワーク
Richard B Jones1, Andrew Gordus, Jordan A Krall
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature
|November 8, 2005
まとめ
この研究では,ErbB受容体とのタンパク質の相互作用をマッピングし,新しい結合と,がんにおける受容体の乱交がタンパク質濃度とどのように関係しているかを明らかにしました. 信号ネットワークの定量的な見方を提供しています.
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.
- バイオケミストリー バイオケミストリー
背景:
- 皮膚表皮成長因子受容体 (EGFR) のシグナル伝達は非常に重要ですが,その初期タンパク質徴募のステップは完全に理解されていません.
- ErbB経路における初期のシグナル伝達イベントに関する全ゲノム的見解は欠けている.
研究 の 目的:
- 4つのErbB受容体のための定量的なタンパク質相互作用ネットワークを作成する.
- ErbBシグナル伝達における最も初期のステップ:活性化受容体へのタンパク質の勧誘を調査する.
主な方法:
- ヒトSrcホモロジー2 (SH2) およびフォスフォチロジン結合 (PTB) ドメインを含むタンパク質マイクロアレイを使用した.
- ErbB受容体における61のフォスフォチロジンペプチドの均衡解離定数を測定し,77,592の生化学分析を行った.
主要な成果:
- 定量的なタンパク質相互作用ネットワークを生成し,現在のドメイン選択性の理解を超えた新しい相互作用を明らかにしました.
- ErbB受容体間の差異的乱交が観察されました;EGFRとErbB2は,ErbB3とは異なり,より低い親和度値でより乱交になります.
結論:
- 濃度に依存する受容体乱交の変化は,EGFRやErbB2のような受容体チロシンキナーゼの腫瘍性潜在性に寄与する可能性がある.
- この研究は,信号ネットワークのダイナミクスと潜在的な癌メカニズムに関する新しい視点を提供しています.
関連する概念動画
Protein-protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...


