Membrane estrogen receptors bind SRC

Stable Identifier
Reaction [binding]
Homo sapiens
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Rapid signaling downstream of estrogen stimulation activates signaling through MAP kinase and PI3K/AKT signaling pathways, as well as initiating cross-talk with NF kappa beta and receptor tyrosine kinase pathways (reviewed in Hammes et al, 2007; Handa et al, 2012; Lange et al, 2017; Losel et al, 2003). Signaling through AKT regulates cell cycle progression through CREB-mediated upregulation of cyclin D1 and depends on recruitment of SRC and the p85 regulatory subunit of PI3K (Castoria et al, 2001; Marino et al, 2002; Marino et al, 2003; Castoria et al, 2012; reviewed in Castoria et al, 2010). Estrogen-stimulated nitric oxide (NO) release from endothelial cells likewise depends on the recruitment of SRC to the estrogen receptors at the plasma membrane (Haynes et al, 2003).
Once recruited, SRC is activated by autophosphorylation at tyrosine 419, which in turn is required for the recruitment and activation of PI3K and AKT, and ultimately for the activation of endothelial nitric oxide synthase (eNOS) and promotion of AKT-dependent cellular proliferation (Haynes et al, 2000; Simoncini et al, 2000; Haynes et al, 2003; Li et al, 2007; reviewed in Kim and Bender, 2005; Hammes and Levin, 2011; Le Romancer et al, 2011: Castoria et al, 2010). Formation of an eNOS signaling complex also depends on interaction between the estrogen receptor and heterotrimeric G-proteins (Wyckoff et al, 2001; reviewed in Schwartz, 2016).
Literature References
PubMed ID Title Journal Year
17921256 Variant estrogen receptor-c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation

Baron, R, Haynes, MP, Collinge, M, Li, L, Sessa, WC, Sanjay, A, Hisamoto, K, Bauer, PM, Bender, JR, Kim, KH

Proc. Natl. Acad. Sci. U.S.A. 2007
21851428 Roles for oestrogen receptor β in adult brain function

Handa, RJ, Wang, JM, Herbison, AE, Ogawa, S

J. Neuroendocrinol. 2012
12511868 Nongenomic actions of steroid hormones

Wehling, M, Lösel, R

Nat. Rev. Mol. Cell Biol. 2003
19879889 Cell proliferation regulated by estradiol receptor: Therapeutic implications

Auricchio, F, Giovannelli, P, Castoria, G, Migliaccio, A

Steroids 2010
15956360 Rapid, estrogen receptor-mediated signaling: why is the endothelium so special?

Bender, JR, Kim, KH

Sci. STKE 2005
22028449 Minireview: Recent advances in extranuclear steroid receptor actions

Hammes, SR, Levin, ER

Endocrinology 2011
12431978 Src kinase mediates phosphatidylinositol 3-kinase/Akt-dependent rapid endothelial nitric-oxide synthase activation by estrogen

Baron, R, Haynes, MP, Collinge, M, Li, L, Sessa, WC, Hisamoto, K, Bender, JR, Russell, KS, Sinha, D

J. Biol. Chem. 2003
11029403 Membrane estrogen receptor engagement activates endothelial nitric oxide synthase via the PI3-kinase-Akt pathway in human endothelial cells

Fulton, D, Haynes, MP, Collinge, M, Sessa, WC, Russell, KS, Morales-Ruiz, M, Bender, JR, Sinha, D

Circ. Res. 2000
17037979 Integration of rapid signaling events with steroid hormone receptor action in breast and prostate cancer

Marker, PC, Hammes, SR, Gioeli, D, Lange, CA

Annu. Rev. Physiol. 2007
17916740 Extranuclear steroid receptors: nature and actions

Hammes, SR, Levin, ER

Endocr. Rev. 2007
11369763 Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i)

Mendelsohn, ME, Yuhanna, IS, Mumby, SM, Mineo, C, Wyckoff, MH, Chambliss, KL, Shaul, PW

J. Biol. Chem. 2001
12808053 Biphasic estradiol-induced AKT phosphorylation is modulated by PTEN via MAP kinase in HepG2 cells

Marino, M, Trentalance, A, Acconcia, F

Mol. Biol. Cell 2003
22266855 Tyrosine phosphorylation of estradiol receptor by Src regulates its hormone-dependent nuclear export and cell cycle progression in breast cancer cells

Auricchio, F, Migliaccio, A, Castoria, G, De Rosa, C, Barone, MV, de Falco, A, Giraldi, T, Abbondanza, C, Giovannelli, P, Lombardi, M

Oncogene 2012
12388769 Distinct nongenomic signal transduction pathways controlled by 17beta-estradiol regulate DNA synthesis and cyclin D(1) gene transcription in HepG2 cells

Marino, M, Trentalance, A, Acconcia, F, Weisz, A, Bresciani, F

Mol. Biol. Cell 2002
11029009 Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase

Liao, JK, Brazil, DP, Ley, K, Hafezi-Moghadam, A, Simoncini, T, Chin, WW

Nature 2000
27288742 Rapid steroid hormone actions via membrane receptors

Verma, A, Schwartz, Z, Bivens, CB, Schwartz, N, Boyan, BD

Biochim. Biophys. Acta 2016
21680538 Cracking the estrogen receptor's posttranslational code in breast tumors

Poulard, C, Corbo, L, Renoir, JM, Sentis, S, Cohen, P, Le Romancer, M

Endocr. Rev. 2011
11689445 PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells

Auricchio, F, Fiorentino, R, Di Domenico, M, Barone, MV, Bilancio, A, de Falco, A, Lombardi, M, Castoria, G, Migliaccio, A, Varricchio, L

EMBO J. 2001
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