Requirements for estrogen receptor at membrane localization and function
Requirements for estrogen receptor at membrane localization and function
复制标题
DOI：
10.1016/j.steroids.2005.02.015
复制
发表时间：
2005-05-01
期刊：
影响因子：
2.7
通讯作者：
Levin, ER
中科院分区：
文献类型：
--
作者：
Evinger, AJ;Levin, ER
雌激素受体 a (ER(x)) 作为质膜上的功能受体而存在。其定位和功能的结构要求尚不清楚。一些实验室最近阐明了某些要求。我们最近发现，在缺乏雌激素的情况下，ER α 向膜的易位依赖于 ERa 蛋白的 Caveolin-1 和丝氨酸 522。丝氨酸 522 突变为丙氨酸会导致膜定位和与同样，caveolin-1 支架结构域（氨基酸 60-100）的缺失很大程度上阻止了 ER α 在质膜上的定位。在存在雌二醇（EA ERU、Src 同源性和胶原同源性 (Shc)）和胰岛素样生长因子受体 1 蛋白的情况下，这些蛋白与 ERa 结合并增加了膜上的定位。膜定位的 ER(x 作为非典型 G 蛋白偶联受体发挥作用。没有好的方法。有证据表明 ERa 跨越细胞膜或含有细胞外结构域，以与细胞环境相关的方式激活不同的 G 蛋白。在乳腺癌中，Src 会激活基质金属蛋白酶-2 和 -9，从而裂解肝素结合表皮生长因子，从而激活 EGFR。激酶，赋予细胞生长和存活 Crown 版权所有 (c) 2005 由 Elsevier Inc 出版。保留所有权利。
The estrogen receptor a (ER(x) exists as a functional receptor at the plasma membrane. The structural requirements for localization and function are not well understood. Several laboratories have recently elucidated certain requirements. We recently found the translocation of ER alpha to the membrane in the absence of estrogen is dependent on caveolin-1 and serine 522 of the ERa protein. Mutation of serine 522 to alanine results in a 62% decrease in membrane localization and association with caveolin-1. Similarly, deletion of the caveolin-1 scaffolding domain (amino acids 60-100) largely prevents the localization of ER alpha at the plasma membrane. In the presence of estradiol (EA ERU, Src-homology and collagen homology (Shc), and insulin-like growth factor receptor-1 proteins associate with and increase the localization of ERa at the membrane. Membrane-localized ER(x functions as an atypical G-protein coupled receptor. There is no good evidence that ERa spans the membrane or contains an extracellular domain. E-2/ER alpha activates different G-proteins in cell context-related fashion. These G-proteins lead to the activation of Src through PLC, PKC, IP3 and calcium influx. In breast cancer, Src activates matrix metalloprotemase-2 and -9, which cleaves heparin binding epidermal growth factor, and thus activates EGFR. This leads to downstream signaling through ERK and P13 kinase, imparting cell growth and survival. Crown Copyright (c) 2005 Published by Elsevier Inc. All rights reserved.