G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology

Classical signaling pathways activated by GPER. GPER binds to its endogenous ligands (estrogen and aldosterone), leading to multiple downstream cascades, including ERK, PI3K/AKT, AMPK/PKA, and NF-kB pathways. Activation of Src via GPER results in the release of matrix metalloproteinase (MMP) mediation of heparin-binding epidermal growth factor (HB-EGF) cleavage, followed by transactivation of the EGF receptor (EGFR), which in turn causes the activation of extracellular signal-regulated kinases (ERK) and the activation of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase (PI3K/AKT). GPER stimulates the AMPK signaling pathway, which increases adenylyl cyclase (AC) activity to stimulate the cAMP-activated downstream protein kinase A (PKA) signal pathway that inhibits ERK. GPER also reduces the phosphorylation, nuclear localization, and transcriptional activity of the NF-κB pathway.

Publication

The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology. (2023) Fujie Xu, et al. Biomolecules. 2023 Sep;13(9):1410. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

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