SHC1 is phosphorylated downstream of estrogen stimulation of GPER1

Stable Identifier
R-HSA-9624014
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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SHC1 is phosphorylated downstream of estrogen stimulation of GPER1
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E2 treatment stimulates phosphorylation of MAPK3 and MAPK1 (also known as ERK1 and ERK2) downstream of GPER1 in a SRC- and G-protein beta gamma complex-dependent manner (Filardo et al, 2000; Quin et al, 2009). ERK phosphorylation through this pathway is mediated by SRC-dependent phosphorylation of the SHC adaptor protein, consistent with G beta gamma signaling in other pathways (Filardo et al, 2000; Quinn et al, 2009; Touhara et al, 1995; van Biesen et al, 1995; Luttrell et al, 1996; reviewed in Filardo and Thomas, 2012). Estrogen-dependent signaling through the G beta gamma -SRC -SHC module establishes crosstalk with integrin alpha5beta2 pathway and ultimately cross-talks with EGFR signaling, activating MAPK phosphorylation (reviewed in Filardo and Thomas, 2012; Prossnitz and Barton, 2014; Gaudet et al, 2015; Filardo et al, 2018). The mechanisms by which SRC and G beta gamma impinge on SHC phosphorylation are not fully elucidated, and direct phosphorylation of SHC by SRC has not been demonstrated in this pathway.
Literature References
PubMed ID Title Journal Year
24530924 Estrogen biology: new insights into GPER function and clinical opportunities

Prossnitz, ER, Barton, M

Mol. Cell. Endocrinol. 2014
7651538 Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway

Luttrell, DK, Krueger, KM, Luttrell, LM, Sakaue, M, Lefkowitz, RJ, van Biesen, T, Hawes, BE, Porfiri, E, Touhara, K

Nature 1995
22495674 Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology

Thomas, P, Filardo, EJ

Endocrinology 2012
19342448 Coordinate regulation of estrogen-mediated fibronectin matrix assembly and epidermal growth factor receptor transactivation by the G protein-coupled receptor, GPR30

Schwarzbauer, JE, Frackelton, AR, Kim, M, Filardo, EJ, Graeber, CT, Quinn, JA

Mol. Endocrinol. 2009
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
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
8702633 Role of c-Src tyrosine kinase in G protein-coupled receptor- and Gbetagamma subunit-mediated activation of mitogen-activated protein kinases

Luttrell, DK, Luttrell, LM, Lefkowitz, RJ, van Biesen, T, Lansing, TJ, Hawes, BE

J. Biol. Chem. 1996
7568118 G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein

Lefkowitz, RJ, van Biesen, T, Hawes, BE, Touhara, K

Proc. Natl. Acad. Sci. U.S.A. 1995
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein tyrosine kinase activity of unknown kinase [cytosol]

Physical Entity
unknown kinase [cytosol] (Homo sapiens)
Activity
protein tyrosine kinase activity (GO:0004713)
This event is regulated
Positively by
Regulator
G-protein beta-gamma complex [plasma membrane] (Homo sapiens)
Regulator
MyrG-p-Y419-SRC [plasma membrane] (Homo sapiens)
Authored
Rothfels, K  (2018-12-15)
Reviewed
Marino, M  (2019-04-24)
Acconcia, F  (2019-04-24)
Created
Rothfels, K  (2018-10-06)
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