Meta-Biol

• Pathways

ESR1-mediated signaling can be initiated in an estrogen-independent manner downstream of stimuli such as EGF, NRG1, IGF, insulin, dopamine and cAMP (Ignar-Trowbridge et al, 1993, Pietras et al, 1995; Ma et al, 1994; Newton et al, 1994; Smith et al, 1993; Aronica and Katzenellenbogen, 1993). Stimulation with EGF or IFGF-1 promotes the MAPK-dependent phosphorylation of ESR1 at serine 118, which contributes to interaction with CBP/p300 and the p160 family of coactivators (Bunone et al, 1996; Chen et al, 2002; Cheng et al, 2007; reviewed in Anbalagan and Rowan, 2105). Serine 118 is also phosphorylated in response to estrogen stimulation (Chen et al, 2002; reviewed in Anbalagan and Rowan, 2015).
The relationship between MAPK-dependent S118 phosphorylation of ESR1 and the release from the cochaperone complex and ESR1 dimerization is not clear. In this reaction, all these events are shown happening simultaneously.