Figure 10.
Proposed mechanism by which estradiol produces bidirectional effects on CREB phosphorylation. Via interactions with classical estrogen receptors localized at the neuronal membrane, estradiol activates both group I and group II mGluR signaling. In one case, estradiol stimulation of mGluR1a leads to PLC/MAPK-induced CREB phosphorylation. Concurrently, activation of group II mGluR signaling decreases L-type calcium channel-dependent CREB phosphorylation through Gi/o inhibition of AC and PKA. The shaded arrows indicate decreased activity. CaM, Calmodulin; RSK, p90 ribosomal protein S6 kinase; CaMKIV, calmodulin-dependent protein kinase IV.