Figure 2

ER regulation by a variety of signals. Growth factors such as epidermal growth factor, insulin-like growth factor-1, insulin, and transforming growth factor-β bind to and activate their receptors, which in turn activate the RAS–RAF–ERK and the phosphoinositide 3-kinase (PI3K) pathways; the activated kinases then phosphorylate and activate ER. Other extracellular stimuli such as dopamine and cyclic AMP bind G-protein-coupled receptors and activate adenylyl cyclase (AC) and protein kinase A (PKA), which subsequently phosphorylate and activate ER. ER can also interact directly with components of the cytosolic signaling molecules, including the regulatory subunit of PI3K, leading to the activation of the serine/threonine kinase Akt. In the nucleus, hormone binding results in receptor dimerization and recruitment of coactivators or corepressors depending on the bound ligand, leading to transcriptional activation or repression. ERE, estrogen response element; MEK, MAP kinase/ERK kinase; SERM, selective estrogen receptor modulator.