Helicobacter pylori Suppresses Glycogen Synthase Kinase 3β to Promote β-Catenin Activity
Helicobacter pylori Suppresses Glycogen Synthase Kinase 3β to Promote β-Catenin Activity
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DOI：
10.1074/jbc.m801818200
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发表时间：
2008-10-24
影响因子：
4.8
通讯作者：
Naumann, Michael
中科院分区：
文献类型：
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作者：
Sokolova, Olga;Bozko, Przemyslaw M.;Naumann, Michael
人类病原体幽门螺杆菌影响细胞粘附、增殖和凋亡，并参与胃腺癌的形成。在我们的研究中，我们分析了幽门螺杆菌感染对β -连环蛋白调控的影响，β -连环蛋白在细胞粘附和肿瘤发生中都起着核心作用。H. pylori感染Madin-Darby犬肾细胞，可抑制Ser/Thr磷酸化和β -连环蛋白泛素依赖性降解，上调淋巴细胞增强因子/T细胞因子（LEF/TCF）依赖性转录。β -连环蛋白的丝氨酸/苏氨酸磷酸化受损伴随着糖原合成酶激酶3 β磷酸化的增加。Akt激酶是糖原合成酶激酶3 β的上游调节因子，被特异性抑制剂Akti-1/2抑制或用siRNA耗尽Akt可恢复β -连环蛋白的丝氨酸/苏氨酸磷酸化。我们得出结论，糖原合成酶激酶3 β活性在幽门螺旋杆菌感染的犬肾细胞中β -连环蛋白调控和LEF/TCF转激活中发挥重要作用。
The human pathogen Helicobacter pylori influences cell adhesion, proliferation, and apoptosis and is involved in gastric adenocarcinoma formation. In our study we analyzed the impact of H. pylori infection on the regulation of beta-catenin, which plays a central role in both cell adhesion and tumorigenesis. Infection of Madin-Darby canine kidney cells with H. pylori led to suppression of Ser/Thr phosphorylation and ubiquitin-dependent degradation of beta-catenin and to up-regulation of lymphoid enhancer-binding factor/T cell factor (LEF/TCF)dependent transcription. The impaired Ser/Thr phosphorylation of beta-catenin was accompanied by an increase of glycogen synthase kinase 3 beta phosphorylation. Inhibition of Akt kinase, an up-stream regulator of glycogen synthase kinase 3 beta by a specific inhibitor Akti-1/2 or depletion of Akt with siRNA restored Ser/Thr phosphorylation of beta-catenin. We conclude that glycogen synthase kinase 3 beta activity exerts an important role in beta-catenin regulation and LEF/TCF transactivation in H. pylori-infected Madin-Darby canine kidney cells.