Reactome | GPER:Heterotrimeric G-protein Gs binds ESTG

GPER:Heterotrimeric G-protein Gs binds ESTG

Stable Identifier

R-HSA-9036307

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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GPER:Heterotrimeric G-protein Gs binds ESTG

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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).
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).

Literature References

PubMed ID	Title	Journal	Year
17379646	Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane Filardo, E J, Pang, Y, Thomas, P, Quinn, J, Dong, J, Shaw, S, Graeber, C	Endocrinology	2007
15539556	Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells Pang, Y, Thomas, P, Dong, J, Filardo, E J	Endocrinology	2005
15705806	A transmembrane intracellular estrogen receptor mediates rapid cell signaling Prossnitz, ER, Revankar, CM, Sklar, LA, Arterburn, JB, Cimino, DF	Science	2005
26987903	Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1 Tran, P, Matnishian, V, Giles, J, Burgard, MA, Firkins, R, Tran, QK, Francis, S, Gebert-Oberle, B, Jasurda, J, VerMeer, M	J. Biol. Chem.	2016
18566127	G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol Klewer, M, Rohde-Schulz, B, Fritzemeier, KH, Otto, C, Bader, B, Fuchs, I, Brittain, D, Nubbemeyer, R, Schwarz, G, Prelle, K, Langer, G	Endocrinology	2008
11043579	Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF Frackelton, AR, Bland, KI, Filardo, EJ, Quinn, JA	Mol. Endocrinol.	2000
16645038	Nature of functional estrogen receptors at the plasma membrane Levin, ER, Razandi, M, Pedram, A	Mol. Endocrinol.	2006
26190834	The G-protein coupled estrogen receptor, GPER: The inside and inside-out story Gaudet, HM, Christensen, EM, Cheng, SB, Filardo, EJ	Mol. Cell. Endocrinol.	2015
28595943	A role for G-protein coupled estrogen receptor (GPER) in estrogen-induced carcinogenesis: Dysregulated glandular homeostasis, survival and metastasis Filardo, EJ	J. Steroid Biochem. Mol. Biol.	2018
11773440	Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis Bland, KI, Frackelton, AR, Filardo, EJ, Quinn, JA	Mol. Endocrinol.	2002
19931550	Conserved estrogen binding and signaling functions of the G protein-coupled estrogen receptor 1 (GPER) in mammals and fish Pang, Y, Thomas, P, Dong, J, Peyton, C, Alyea, R, Berg, AH	Steroids	2010