機能的に異なるGタンパク質は,同じ細胞内のPI水解に異なる受容体を選択的にカップリングします
A Ashkenazi1, E G Peralta, J W Winslow
1Department of Molecular Biology Genentech, Inc., South San Francisco, California 94080.
Cell
|February 10, 1989
まとめ
細胞は複数のGタンパク質 (Gp) を用いてフォスフォリファースCを活性化し,選択的に異なる受容体に結合します. このGタンパク質の多様性は,フォスホイノシチドの水解を調節することによって,細胞の反応を微調整する.
科学分野:
- 細胞の信号伝達経路は,
- Gタンパク質に結合した受容体.
- 信号伝達メカニズム 信号伝達メカニズム
背景:
- Gタンパク質の既知の機能は,分子クローニングによって特定された数と一致しません.
- 細胞過程における異なるGタンパク質の特定の役割を理解することは極めて重要です.
研究 の 目的:
- 複数のGタンパク質が異なる受容体と結合することで,フォスフォリファースC活性化などの同じ機能を媒介できるかどうかを調査する.
- これらのGタンパク質 (Gp) とその選択的受容体結合を特徴づける.
- Gp経路が細胞応答にどのように影響するかを決定する.
主な方法:
- 分子クローニングを使用して,細胞に受容体を導入します.
- フォスフォリファースC活性化とフォスフォイノシチド (PI) の水解を評価する.
- 百日咳毒素の感受性を用いてGタンパク質を区別する.
- 受容体経路の割り当てを確認するために,PIの水解反応の添加性関係を分析する.
主要な成果:
- 細胞には複数のGタンパク質 (Gp) が存在し,フォスフォリファースCを活性化しますが,異なる受容体 (内生性または変異性) と選択的に結合します.
- Gp経路は, pertussis toxinに対する感受性によって区別することができます.
- PI水解反応の添加性は,特定の受容体-Gp経路の割り当てを確認しました.
- 異なるGp経路は,著しく異なる量のPI水解を活性化させ,C.フォスフォリファーゼへの結合効率が異なることを示している.
結論:
- 特定のGp経路は,単一の細胞内に存在し,異なる受容体を選択的にフォスフォリファースC活性化に結びつける.
- これらのGp経路は,PI水解の大きさを調節することによって,様々な細胞外信号に対する細胞反応の特異性に寄与する.
関連する概念動画
G-protein Coupled Receptors
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G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...


