PI3K binds membrane-associated estrogen receptors

Stable Identifier
Reaction [binding]
Homo sapiens
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PI3K is recruited to the estrogen receptors at the plasma membrane by virtue of an estrogen-dependent interaction of the p85 regulatory subunit with the estrogen receptor. Estrogen stimulation increases PI3K activity in a manner that also depends on SRC and SRC kinase activity, and results in increased PIP3 production and activation of AKT signaling (Simoncini et al, 2000; Castoria et al, 2001; Castoria et al, 2012; Le Romancer et al, 2008). Activation of AKT signaling downstream of estrogen stimulation drives cellular proliferation through the upregulation of the G1/S cyclin CCND1 (Castoria et al, 2001; Castoria et al, 2004; reviewed in Castoria et al, 2010), and E2 is also required for recruitment of focal adhesion kinase (FAK, also known as PTK2) (Le Romancer et al, 2008). AKT activation additionally stimulates phosphorylation of eNOS at residue 1117, promoting NO release in endothelial cells (Simoncini et al, 2000; Haynes et al, 2000; Hisamoto et al, 2001; Li et al, 2003; Haynes et al, 2003; reviewed in Levin, 2011).
Literature References
PubMed ID Title Journal Year
12682286 Plasma membrane localization and function of the estrogen receptor alpha variant (ER46) in human endothelial cells

Haynes, MP, Li, L, Bender, JR

Proc. Natl. Acad. Sci. U.S.A. 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
15314172 Role of atypical protein kinase C in estradiol-triggered G1/S progression of MCF-7 cells

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

Mol. Cell. Biol. 2004
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
25587652 Extranuclear steroid receptors are essential for steroid hormone actions

Levin, ER

Annu. Rev. Med. 2015
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
20861220 Minireview: Extranuclear steroid receptors: roles in modulation of cell functions

Levin, ER

Mol. Endocrinol. 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
11044445 Estrogen induces the Akt-dependent activation of endothelial nitric-oxide synthase in vascular endothelial cells

Tasaka, K, Hisamoto, K, Adachi, K, Kurachi, H, Murata, Y, Taniguchi, N, Nishio, Y, Fujiwara, N, Ohmichi, M, Hayakawa, J, Kanda, Y, Miyoshi, E

J. Biol. Chem. 2001
18657504 Regulation of estrogen rapid signaling through arginine methylation by PRMT1

Leconte, N, Robin-Lespinasse, Y, Gobert-Gosse, S, Bouchekioua-Bouzaghou, K, Goddard, S, Corbo, L, Sentis, S, Treilleux, I, Le Romancer, M

Mol. Cell 2008
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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