活性化されたEGF受容体とコーティングされたピットアダプチンとの相互作用
1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.
まとめ
エピダーマル成長因子 (EGF) 受容体は,内皮細胞分裂 (endocytosis) 中のコーティングピットアセンブリの前にアルファ-アダプチンと結合する. 細胞の吸収に不可欠なこの相互作用は,コーティングピットが完全に形成される前に起こります.
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 (EGF) 受容体は,細胞信号伝達の重要な媒介体である.
- エンドサイトーシスは,分子内化のための基本的な細胞プロセスです.
- アダプタータンパク質は,タンパク質の密輸と膜動力学において重要な役割を果たします.
研究 の 目的:
- EGF受容体とアダプタータンパク質の相互作用を研究する.
- この相互作用に関与するアルファアダプチンの特定の領域を特定する.
- コーティングピット形成に相対する受容体-アダプチン結合のタイミングを決定する.
主な方法:
- EGFで治療されたA-431細胞を用いた共免疫プレシピテーションアッセイ.
- 温度の変化実験 (37°C vs. 4°C) を行い,エンドサイトーシスを研究した.
- アルファ・アダプチンの部分タンパク質分解により,相互作用領域をマップする.
- エンドサイトーシスを抑制し,組み立て前イベントを研究するために,カリウム枯渇.
主要な成果:
- アルファアダプチンの約50%は,EGF受容体と37°Cで共免疫的に precipitated,しかし4°Cではない.
- 部分タンパク質分解は,α-アダプチンのアミノ端末ドメインがEGF受容体との関連を媒介することを示した.
- レセプター-アダプチン結合は,カリウム欠乏した細胞で増加し,完全なコーティングピットアセンブリに先行することを示唆しています.
結論:
- レセプター-アダプチン結合は,コーティングされたピッツの完全な組み立ての前に,無傷の細胞で発生します.
- アルファ-アダプチンのアミノ端末ドメインは,EGF受容体との結合に不可欠です.
- この相互作用は,EGF受容体の内細胞経路における重要な早期イベントである.
関連する概念動画
Coat Assembly and GTPases
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Activation and Inactivation of G Proteins
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...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...


