Figure 14.

A schematic diagram showing the relationships among JNK activation, Hes-1 expression and phosphorylation, GluR1 expression, and AMPA-evoked calcium influx in cortical neurons. A stimulus, such as oxidative stress, would activate JNK1 signaling. JNK1 activation directly phosphorylates Hes-1 at Ser-263. Hes-1 phosphorylation at this residue results in stabilization of the Hes-1 protein. Upon direct binding to the N-boxes of the GluR1 promoter and through preventing Mash1/E47 complex from binding to the E-boxes of the GluR1 promoter, Hes-1 decreased GluR1 expression that leads to decreased calcium influx evoked by AMPA in cortical neurons.