Abstract
Protein phosphatase-2A (PP2A) activity is significantly suppressed in Alzheimer’s disease. We have reported that glycogen synthase kinase-3β (GSK-3β) inhibits PP2A via upregulating the phosphorylation of PP2A catalytic subunit (PP2AC). Here we studied the effects of GSK-3β on the inhibitory demethylation of PP2A at leucine-309 (dmL309-PP2AC). We found that GSK-3β regulates dmL309-PP2AC level by regulating PME-1 and PPMT1. Knockdown of PME-1 or PPMT1 eliminated the effects of GSK-3β on PP2AC. GSK-3 could negatively regulate PP2A regulatory subunit protein level. We conclude that GSK-3β can inhibit PP2A by increasing the inhibitory L309-demethylation involving upregulation of PME-1 and inhibition of PPMT1.
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