The predictive protein structure of GPER and its intracellular downstream non-genomic signaling pathways (IMAGE)

Compuscript Ltd

The predictive protein structure of GPER and its intracellular downstream non-genomic signaling pathways

Caption

(A) The AlphaFold protein structure of GPER from the public database (https://alphafold.com/entry/Q99527).

(B) E2, the GPER-specific agonist G1, SERMs, and SERDs activate GPER, which is predominantly localized at the cell membrane or intracellularly at the endoplasmic reticulum. GPER activates several heterotrimeric G proteins, leading to the activation of SRC, which further induces the activation of MMPs, cleaves HB-EGF, and releases free HB-EGF. HB-EGF then transactivates the EGFR, which in turn activates the downstream pathways of MAPK/ERK and PI3K/AKT, inducing gene transcription (such as c-Fos, pS2, cyclin A, cyclin D1, and cyclin E) and regulating ion channels (such as Ca2+, Na+, and K+). Other G protein-activated multiple downstream cascades include the activation of AC and the production of cAMP, followed by the activation of the PKA/CREB axis. The mobilization of Ca2+ from intracellular stores activates the PLC/PKC axis. The above signalings co-regulate downstream gene expression and promote tumor growth, invasion, metastasis, and clinical drug resistance. GPER, G protein-coupled estrogen receptor; SERMs, selective ER modulators; SERDs, selective ER downregulators; MMPs, matrix metalloproteinases; HB-EGF, heparin-binding epidermal growth factor; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; PI3K, phosphoinositide 3-kinase; AKT, protein kinase B; AC, adenylate cyclase; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; CREB, cAMP-response element binding protein; PLC, phospholipase C; PKC, protein kinase C.

Credit

Tenghua Yu, Chongwu He, Hui Zhang, Yi Zhu, Annie Wang, Xiaoqiang Zeng, Yanxiao Huang, Jiamin Zhong, Xingye Wu, Yi Shu, Guowei Shen, Chao Yu, Ke Zhou, Usman Zeb, Rebeka Dejenie, Yan Peng, Rex C. Haydon, Hue H. Luu, Russell R. Reid, Tong-Chuan He, Jiaming Fan, Jingjing Li

Usage Restrictions

Credit must be given to the creator. Only noncommercial uses of the work are permitted. No derivatives or adaptations of the work are permitted.

License

CC BY-NC-ND

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.