Membrane ER mediated induction of MAPK activity was reported in different cell types. Estrogen stimulated MAPK activation through c–Src phosphorylation and the subsequent activation of Shc and Ras. This led to an increase in ERK phosphorylation in neocortical explants from ERα knockout mice (ERKO) (Nethrapalli et al. 2001). In septal–derived cholinergic SN56 cells a membrane ER was found to modulate neuroprotection against beta–amyloid toxicity through the activation of Raf–1/MEK/ERK1/2 pathway (Andreozzi et al. 2004).