Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, MS-130, Houston, TX 77030, USA.
Steroids. 2011 Aug;76(9):877-84. doi: 10.1016/j.steroids.2011.02.017. Epub 2011 Feb 25.
Estrogen mediates biological effects on cell proliferation, differentiation, and homeostasis through estrogen receptor (ER). In addition to functioning as a ligand-activated nuclear transcription factor to directly regulate gene transcription, ER also mediates rapid activation of signaling pathways independent of its transcriptional activity. A subpopulation of ER localized to the cell membrane or cytoplasm has been proposed to mediate ER activation of signaling pathways. This review focuses on recent advances in our understanding of mechanisms responsible for ER cytoplasm/membrane localization, where rapid extra-nuclear signaling is initiated. These mechanisms include lipid modification of the receptor (palmitoylation) and interactions with membrane and cytoplasmic adaptor proteins including caveolins, striatin, p130Cas, Shc, HPIP, MTA-1s, and MNAR/PELP1. While it is clear that ER mediates rapid extra-nuclear signaling resulting in activation of signaling pathways such as Src/MAPK and PI-3 kinase/Akt, how ER extra-nuclear signaling influences overall ER/estrogen physiology is still not well understood. Future studies defining physiological roles of ER extra-nuclear actions and crosstalk with its nuclear counterparts will be important to our overall understanding of estrogen and ER biological functions.
雌激素通过雌激素受体 (ER) 介导细胞增殖、分化和稳态的生物学效应。除了作为配体激活的核转录因子直接调节基因转录外，ER 还介导不依赖其转录活性的信号通路的快速激活。已经提出 ER 的一个亚群定位于细胞膜或细胞质中，以介导 ER 对信号通路的激活。这篇综述重点介绍了我们对 ER 细胞质/膜定位负责的机制的最新理解，其中快速的核外信号开始启动。这些机制包括受体的脂质修饰（棕榈酰化）以及与质膜和细胞质衔接蛋白的相互作用，包括 caveolins、striatin、p130Cas、Shc、HPIP、MTA-1s 和 MNAR/PELP1。虽然很明显 ER 介导快速的核外信号，导致信号通路如 Src/MAPK 和 PI-3 激酶/Akt 的激活，但 ER 核外信号如何影响 ER/雌激素的整体生理学仍不清楚。未来研究确定 ER 核外作用的生理作用及其与核对应物的串扰对于我们全面理解雌激素和 ER 的生物学功能将是重要的。
