ESTG-stimulated dissociation of GPER:heterotrimeric G-protein (s) complex

Stable Identifier
R-HSA-9036308
Type
Reaction [dissociation]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
ESTG-stimulated dissociation of GPER:heterotrimeric G-protein (s) complex
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Stimulation of GPER through E2 binding activates nucleotide exchange on heterotrimeric G-protein and subsequent release of G alpha (s) and G beta-gamma subunits. G alpha (s) stimulates adenylate cyclase and activates PKA through elevated cAMP levels, while the G beta-gamma complex transactivates EGFR signaling by releasing HB-EGF in a matrix-metalloprotease dependent fashion (Filardo et al, 2007; Filardo et al, 2002; Kanda and Watanabe, 2003; Thomas et al, 2005, Filardo et al, 2000; Ding et al, 2009; reviewed in Gaudet et al, 2015; Alexander et al, 2017; Filardo, 2018). In breast cancer cell lines and human keratinocytes, E2-stimulation of GPER results in elevated cAMP levels downstream of G alpha (s) in a PKA dependent-fashion (Filardo et al, 2002; Kanda and Watanabe, 2003; Kanda and Watanabe, 2004). In contrast, in HEK, MDCK and CHO cell lines, no E2-dependent increase in cAMP was observed, and GPER was found to constitutively repress cAMP production in an AKAP5-dependent manner. The reasons for these differences are unclear (Broselid et al, 2014; Gonzalez de Valdivia et al, 2017).
Literature References
PubMed ID Title Journal Year
15539556 Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells

Thomas, P, Pang, Y, Filardo, E J, Dong, J

Endocrinology 2005
17379646 Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane

Filardo, E J, Quinn, J, Pang, Y, Graeber, C, Shaw, S, Dong, J, Thomas, P

Endocrinology 2007
14675202 17beta-estradiol inhibits oxidative stress-induced apoptosis in keratinocytes by promoting Bcl-2 expression

Kanda, N, Watanabe, S

J. Invest. Dermatol. 2003
19741198 Estradiol-mediated ERK phosphorylation and apoptosis in vascular smooth muscle cells requires GPR 30

Ding, Q, Gros, R, Limbird, LE, Chorazyczewski, J, Feldman, RD

Am. J. Physiol., Cell Physiol. 2009
15245432 17beta-estradiol stimulates the growth of human keratinocytes by inducing cyclin D2 expression

Kanda, N, Watanabe, S

J. Invest. Dermatol. 2004
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

Filardo, EJ, Quinn, JA, Bland, KI, Frackelton, AR

Mol. Endocrinol. 2000
26190834 The G-protein coupled estrogen receptor, GPER: The inside and inside-out story

Gaudet, HM, Cheng, SB, Christensen, EM, 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
27392633 Emerging roles for the novel estrogen-sensing receptor GPER1 in the CNS

Alexander, A, Irving, AJ, Harvey, J

Neuropharmacology 2017
28450397 G protein-coupled estrogen receptor 1 (GPER1)/GPR30 increases ERK1/2 activity through PDZ motif-dependent and -independent mechanisms

Gonzalez de Valdivia, E, Broselid, S, Kahn, R, Olde, B, Leeb-Lundberg, LMF

J. Biol. Chem. 2017
24962572 G protein-coupled receptor 30 (GPR30) forms a plasma membrane complex with membrane-associated guanylate kinases (MAGUKs) and protein kinase A-anchoring protein 5 (AKAP5) that constitutively inhibits cAMP production

Broselid, S, Berg, KA, Chavera, TA, Kahn, R, Clarke, WP, Olde, B, Leeb-Lundberg, LM

J. Biol. Chem. 2014
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

Filardo, EJ, Quinn, JA, Frackelton, AR, Bland, KI

Mol. Endocrinol. 2002
Participants
Input
Output
Participates
as an event of
Authored
Rothfels, K  (2018-12-15)
Reviewed
Marino, M  (2019-04-24)
Acconcia, F  (2019-04-24)
Created
Rothfels, K  (2018-02-01)
Cite Us!