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Glycogen synthase kinase-3β regulates leucine-309 demethylation of protein phosphatase-2A via PPMT1 and PME-1》.pdf
FEBS Letters 586 (2012) 2522–2528 journal homepage: www.FEBSL Glycogen synthase kinase-3b regulates leucine-309 demethylation of protein phosphatase-2A via PPMT1 and PME-1 Xiu-Qing Yao 1, Xia-Chun Li 1, Xiao-Xue Zhang, Yang-Yang Yin, Bin Liu, Dan-Ju Luo, Qun Wang, Jian-Zhi Wang, Gong-Ping Liu ⇑ 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 a r t i c l e i n f o a b s t r a c t Article history: Protein phosphatase-2A (PP2A) activity is significantly suppressed in Alzheimer’s disease. We have Received 3 May 2012 reported that glycogen synthase kinase-3b (GSK-3b) inhibits PP2A via upregulating the phosphory- Revised 6 June 2012 lation of PP2A catalytic subunit (PP2AC). Here we studied the effects of GSK-3b on the inhibitory Accepted 8 June 2012 demethylation of PP2A at leucine-309 (dmL309-PP2AC). We found that GSK-3b regulates dmL309- Available online 22 June 2012 PP2AC level by regulating PME-1 and PPMT1. Knockdown of PME-1 or PPMT1 eliminated the effects Edited by Jesus Avila of GSK-3b on PP2AC. GSK-3 could negatively regulate PP2A regulatory subunit protein level. We con- clude that GSK-3b can inhibit PP2A by increasing the inhibitory L309-demethylation involving upregulation of PME-1 and inhibition of PPMT1. Keywords: Glycogen synthase kinase-3b 2012 Federation of E
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