Figure 1

Genomic and nongenomic E2 signaling. In the classical genomic pathway, E2 binds to cytosolic ER, and translocates to the nucleus where it binds directly to the ERE or binds to other transcription factors (TF) tethered to response elements and induces gene transcription. In addition, E2 is able to exert rapid cellular effects through several nongenomic mechanisms. E2 can bind to plasma membrane bound ER and directly activate signaling cascades, such as the PI3K/AKT pathway. Alternatively, upon binding E2, ER can recruit adaptor proteins, which activate signaling cascades. Lastly, E2 can bind nonmembrane bound receptors and directly activate signaling pathways.