甲基乙二醛激活酿酒酵母中的雷帕霉素复合物2-蛋白激酶C信号通路靶点。
Methylglyoxal activates the target of rapamycin complex 2-protein kinase C signaling pathway in Saccharomyces cerevisiae.
作者信息
Nomura Wataru, Inoue Yoshiharu
机构信息
Laboratory of Molecular Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
Laboratory of Molecular Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
出版信息
Mol Cell Biol. 2015 Apr;35(7):1269-80. doi: 10.1128/MCB.01118-14. Epub 2015 Jan 26.
Abstract
Methylglyoxal is a typical 2-oxoaldehyde derived from glycolysis. We show here that methylglyoxal activates the Pkc1-Mpk1 mitogen-activated protein (MAP) kinase cascade in a target of rapamycin complex 2 (TORC2)-dependent manner in the budding yeast Saccharomyces cerevisiae. We demonstrate that TORC2 phosphorylates Pkc1 at Thr(1125) and Ser(1143). Methylglyoxal enhanced the phosphorylation of Pkc1 at Ser(1143), which transmitted the signal to the downstream Mpk1 MAP kinase cascade. We found that the phosphorylation status of Pkc1(T1125) affected the phosphorylation of Pkc1 at Ser(1143), in addition to its protein levels. Methylglyoxal activated mammalian TORC2 signaling, which, in turn, phosphorylated Akt at Ser(473). Our results suggest that methylglyoxal is a conserved initiator of TORC2 signaling among eukaryotes.
摘要
甲基乙二醛是一种源自糖酵解的典型2-氧代醛。我们在此表明，在出芽酵母酿酒酵母中，甲基乙二醛以雷帕霉素复合物2（TORC2）依赖性方式激活Pkc1-Mpk1丝裂原活化蛋白（MAP）激酶级联反应。我们证明TORC2在Thr(1125)和Ser(1143)位点使Pkc1磷酸化。甲基乙二醛增强了Pkc1在Ser(1143)位点的磷酸化，该磷酸化将信号传递至下游的Mpk1 MAP激酶级联反应。我们发现，除了其蛋白质水平外，Pkc1(T1125)的磷酸化状态还影响Pkc1在Ser(1143)位点的磷酸化。甲基乙二醛激活哺乳动物TORC2信号传导，进而使Akt在Ser(473)位点磷酸化。我们的结果表明，甲基乙二醛是真核生物中TORC2信号传导的保守启动子。
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