Reactome | PI3K binds membrane-associated estrogen receptors

PI3K binds membrane-associated estrogen receptors

Stable Identifier

R-HSA-9021660

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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PI3K binds membrane-associated estrogen receptors

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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 Li, L, Haynes, MP, 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 Haynes, MP, Sinha, D, Russell, KS, Collinge, M, Fulton, D, Morales-Ruiz, M, Sessa, WC, Bender, JR	Circ. Res.	2000
15314172	Role of atypical protein kinase C in estradiol-triggered G1/S progression of MCF-7 cells Castoria, G, Migliaccio, A, Di Domenico, M, Lombardi, M, de Falco, A, Varricchio, L, Bilancio, A, Barone, MV, Auricchio, F	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 Castoria, G, Giovannelli, P, Lombardi, M, De Rosa, C, Giraldi, T, de Falco, A, Barone, MV, Abbondanza, C, Migliaccio, A, Auricchio, F	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 Simoncini, T, Hafezi-Moghadam, A, Brazil, DP, Ley, K, Chin, WW, Liao, JK	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 Haynes, MP, Li, L, Sinha, D, Russell, KS, Hisamoto, K, Baron, R, Collinge, M, Sessa, WC, Bender, JR	J. Biol. Chem.	2003
11044445	Estrogen induces the Akt-dependent activation of endothelial nitric-oxide synthase in vascular endothelial cells Hisamoto, K, Ohmichi, M, Kurachi, H, Hayakawa, J, Kanda, Y, Nishio, Y, Adachi, K, Tasaka, K, Miyoshi, E, Fujiwara, N, Taniguchi, N, Murata, Y	J. Biol. Chem.	2001
18657504	Regulation of estrogen rapid signaling through arginine methylation by PRMT1 Le Romancer, M, Treilleux, I, Leconte, N, Robin-Lespinasse, Y, Sentis, S, Bouchekioua-Bouzaghou, K, Goddard, S, Gobert-Gosse, S, Corbo, L	Mol. Cell	2008
11689445	PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells Castoria, G, Migliaccio, A, Bilancio, A, Di Domenico, M, de Falco, A, Lombardi, M, Fiorentino, R, Varricchio, L, Barone, MV, Auricchio, F	EMBO J.	2001