独特の反応経路は,核ホルモン受容体間のアロステル相互作用によって確立されています
B M Forman1, K Umesono, J Chen
1Salk Institute for Biological Studies, San Diego, California, USA.
Cell
|May 19, 1995
まとめ
9-cisレチノ酸受容体 (RXR) を含むような核受容体ヘテロジメは,ユニークなホルモン反応性を示すことができます. アロステリック相互作用は,多様なホルモン反応ネットワークを作り出します.
科学分野:
- 分子生物学は分子生物学である.
- エンドクリノロジー エンドクリノロジー
- 遺伝学 遺伝学とは
背景:
- ヘテロディメリゼーションは,真核細胞の転写因子の基本的メカニズムである.
- 9-cisレチノ酸受容体 (RXR) は,甲状腺ホルモン受容体 (T3R) やレチノ酸受容体 (RAR) のような核受容体の共通のパートナーである.
研究 の 目的:
- 他の核受容体と提携したときにRXRの転写特性を調査する.
- RXRを含むヘテロダイマーが二重ホルモン反応を示すかどうかを判断する.
主な方法:
- 単体およびヘテロダイマーにおける受容体活性を評価するための戦略が開発されました.
- トランスクリプション活動は,T3R,RAR,NGFI-B/Nurr1.1を含む様々なRXRヘテロダイマーについて調べられました.
主要な成果:
- RXRの固有DNA結合は,T3R-RXRとRAR-RXRの異型体において抑制された.
- RXRはNGFI-B/Nurr1孤児受容体との非DNA結合コファクターとして機能した.
- NGFI-B/Nurr1によるヘテロディメリゼーションにより,新たなホルモン依存複合体が形成された.
結論:
- ヘテロダイマー内のアロステリック相互作用は,異なる性質を持つ複合体を生成します.
- Allosteryは,ホルモン反応ネットワークで観察される多様性にとって不可欠です.
関連する概念動画
Intracellular Hormone Receptors
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Types of Receptors: Internal Receptors
Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Target Cell Response to Hormones
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...


