GPER:Heterotrimeric G-protein Gs binds ESTG

GPER1 (G-protein coupled estrogen receptor 1) is an estradiol-binding member of the G-protein coupled receptor family that stimulates rapid non-genomic signaling upon ligand binding (reviewed in Gaudet et al, 2015). Direct binding of E2 to GPER1 remains somewhat controversial, however, with some studies showing high affinity binding of E2 to plasma membranes in a GPER1-transfection dependent manner, and other studies refuting this assertion (Thomas et al, 2005; Revankar et al, 2005; Thomas et al, 2010; Otto et al, 2008; Pedram et al, 2006). In addition to plasma membrane signaling, intracellular E2- and GPER-mediated signaling has also been observed in the endoplasmic reticulum (Revankar et al, 2005).<br>Inactive GPER1 is associated with G alpha s (Filardo et al, 2007). Estrogen stimulation promotes the dissociation of the G protein subunits and initiates downstream signaling through cAMP, MAPK and PI3K pathways, among others (Filardo et al, 2000; Filardo et al, 2002; Tran et al, 2016; reviewed in Gaudet et al, 2015; Filardo, 2018).

GPER1（G-蛋白偶联雌激素受体1）是G-蛋白偶联受体家族中一种雌激素结合成员，在配体结合后可刺激快速的非基因组信号传导（参见Gaudet等，2015年的综述）。然而，E2与GPER1的直接结合仍存在一定争议，部分研究显示E2以高亲和力与GPER1转染依赖性的人血浆膜结合，而另一些研究则对此说法提出质疑（Thomas等，2005年；Revankar等，2005年；Thomas等，2010年；Otto等，2008年；Pedram等，2006年）。除了血浆膜信号传导外，E2和GPER介导的细胞内信号传导亦在粗面内质网中被观察到（Revankar等，2005年）。非活性状态的GPER1与G alpha s（Filardo等，2007年）相关联。雌激素刺激可促进G蛋白亚基的解离，并通过cAMP、MAPK和PI3K等途径启动下游信号传导，相关研究由Gaudet等（2015年）综述，Filardo（2018年）进一步探讨。