文章摘要
杨日云,金晓霞,刘 飞.糖原合酶激酶-3β对蛋白磷酸酯酶2A甲基化的调节[J].南京医科大学学报,2014,(12):1632~1637
糖原合酶激酶-3β对蛋白磷酸酯酶2A甲基化的调节
Glycogen synthase kinase-3β regulates protein phosphatase 2A methylation
投稿时间:2014-07-17  
DOI:10.7655/NYDXBNS20141202
中文关键词: PP2A  PI3K  GSK-3β  LCMT-1
英文关键词: PP2A  PI3K  GSK-3β,LCMT-1
基金项目:国家自然科学基金(30770468)
作者单位
杨日云 南通大学神经再生重点实验室,江苏 南通 226001 
金晓霞 南通大学神经再生重点实验室,江苏 南通 226002 
刘 飞 南通大学神经再生重点实验室,江苏 南通 226003 
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中文摘要:
      目的:研究磷脂酰肌醇3-激酶(phosphoinositide 3-kinases,PI3K)信号通路及其中重要组分糖原合酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)对蛋白磷酸酯酶2A(protein phosphotase 2A,PP2A)甲基化修饰的调节?方法:用分子生物学及药物学手段改变HepG2和HEK-293T细胞中PI3K信号通路及此通路中重要分子GSK-3β的活性,用Western blots分析PI3K信号通路及GSK-3β活性改变对PP2A的催化亚基-C亚基(catalytic subunit C, PP2A-C)甲基化修饰的影响?采用GST-pull down探讨PP2A-C特异性的亮氨酸甲基转移酶(leucine carboxyl methyltransferase-1, LCMT-1)与GSK-3β之间是否存在相互作用?结果:用LY294002下调细胞的PI3K信号通路,促进PP2A-C的甲基化?用GSK-3β抑制剂AR-A014418处理细胞抑制PP2A-C的甲基化?GSK-3β的GST融合蛋白GST-GSK-3β可以pull down LCMT-1?结论:PI3K信号通路参与PP2A催化亚基甲基化的调节,抑制GSK-3β减少PP2A-C的甲基化修饰?GSK-3β与LCMT-1存在相互作用,GSK-3β可能通过LCMT-1,调节PP2A-C的甲基化修饰,进而影响PP2A的活性?
英文摘要:
      Objective:To determine whether and how glycogen synthase kinase-3β (GSK-3β), an important component of phosphoinositide 3-kinases (PI3K) signaling pathway, regulates the methylation of protein phosphotase 2A (PP2A). Methods:By using molecular biological and pharmological approaches to alter the activity of PI3K signaling pathyway and its key molecule, GSK-3β, we investigated the regulation of PI3K pathway and GSK-3β on PP2A methylation by using Western blot analysis in cultured HepG2 and HEK-293T cells,By using GST-pull down, we determined the interaction between LCMT-1 and GSK-3. Results:We found that inhibition of PI3K pathway by PI3K inhibitor LY294002 increased the methylation level of PP2A catalytic subunit. In addition, inhibition of GSK-3β in cells leaded to the less methylation of PP2A catalytic subunit. We found that GST-GSK-3β could pull-down LCMT-1. Conclusion:PI3K signaling pathway is involved in the regulation of PP2A catalytic subunit methylation. Inhibition of GSK-3β suppresses the methylation. GSK-3β has a mutual effect with LCMT-1 and may regulate the methylation of PP2A through LCMT-1.
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