ステロイドホルモン受容体のドーパミンおよびリガンド独立活性化
R F Power1, S K Mani, J Codina
1Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
Science (New York, N.Y.)
|December 13, 1991
まとめ
ステロイドホルモン受容体は,ドーパミンがプロゲステロンを真似するので,リガンドなしで活性化することができます. 鶏のプロゲステロン受容体 (cPR) にある特定のセリン残基は,このリガンド独立活性化の鍵となる.
科学分野:
- 分子内分泌学分子内分泌学
- 神経内分泌学の神経内分泌学
- 遺伝子規制 遺伝子規制
背景:
- ステロイドホルモン受容体は,活性化と遺伝子転写の調節のために伝統的にリガンド結合を必要とします.
- 受容体活性化は,一般的に,リガンド結合イベントにのみ依存していると考えられています.
- 新興の証拠は,受容体活性化のための代替経路を示唆しています.
研究 の 目的:
- ステロイドホルモン受容体のリガンド独立活性化を調査する.
- プロゲステロン受容体の非伝統的な活性化剤としてのドーパミンの役割を調査する.
- ドーパミン媒介の受容体活性化に伴う特定の分子機構を特定する.
主な方法:
- 鶏のプロゲステロン受容体 (cPR) を用いたインビトロ実験.
- 細胞プラズマから核への受容体転位を評価する.
- cPR内の特定のアミノ酸残留物の変異分析.
主要な成果:
- 神経伝達物質であるドーパミンは,リガンド独立の方法でCPRを活性化します.
- ドーパミンは,核へのcPR転位を誘導することによって,プロゲステロンの効果を模倣しました.
- 特定のセリン残留は,ドーパミン依存の活性化には不可欠であるが,プロゲステロン依存の活性化には欠かせないと特定された.
結論:
- ステロイドホルモン受容体は,リガンド独立経路を通じて活性化することができます.
- ドーパミンは,プロゲステロン受容体の機能的アゴニストとして作用し,シグナリングシステム間のクロストークを強調します.
- 特定のアミノ酸残基は,異なる活性化経路を媒介し,受容体調節に関する洞察を提供します.
関連する概念動画
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