Protein SUMOylation has been implicated in the patho
genesis of ischemic stroke. However, the underlyin
g mechanisms remain unclear. Here, we found that
global brain ischemia evokes a sustained elevation of GluK2 SUMOylation in the rat hippocampal CA1 re
gion. Over-expression of wild-type GluK2, but not SUMOylation-deficient mutant, si
gnificantly increased the activity of MLK3 and
JNK3 after kainate stimulation. SUMOylation deficiency attenuated the kainate-stimulated interaction between MLK3 and GluK2. In addition, inhibition of kainate-evoked GluK2 endocytosis decreased the activation of MLK3-JNK3 si
gnalin
g and the bindin
g of MLK3-GluK2 in cultured cortical neurons. These results su
ggest that the internalization of GluK2 followin
g SUMO modification promotes its bindin
g with MLK3, thereby activatin
g the MLK3-JNK3 pathway, which may be responsible for ischemic neuronal cell death.
Structured summary of protein interactions
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