Glycogen synthase kinase-3β regulates leucine-309 demethylation of protein phosphatase-2A via PPMT1 and PME-1.
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 (PP2A(C)). Here we studied the effects of GSK-3β on the inhibitory demethylation of PP2A at leucine-309 (dmL309-PP2A(C)). We found that GSK-3β regulates dmL309-PP2A(C) level by regulating PME-1 and PPMT1. Knockdown of PME-1 or PPMT1 eliminated the effects of GSK-3β on PP2A(C). 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.
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Xiu-Qing
XQ
Yao
Xia-Chun
XC
Li
Xiao-Xue
XX
Zhang
Yang-Yang
YY
Yin
Bin
B
Liu
Dan-Ju
DJ
Luo
Qun
Q
Wang
Jian-Zhi
JZ
Wang
Gong-Ping
GP
Liu
D000544:Alzheimer Disease / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002384:Catalysis; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D007930:Leucine / Q000737:chemistry*; D008745:Methylation; D011497:Protein O-Methyltransferase / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000737:chemistry*
D004791:Enzyme Inhibitors; C524761:LCMT1 protein, human; D011497:Protein O-Methyltransferase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D002265:Carboxylic Ester Hydrolases; C119357:protein phosphatase methylesterase-1; D054648:Protein Phosphatase 2; D007930:Leucine