PP2A Regulatory Subunit PP2A-B′ Counteracts S6K Phosphorylation
PP2A Regulatory Subunit PP2A-B′ Counteracts S6K Phosphorylation
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DOI：
10.1016/j.cmet.2010.03.015
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发表时间：
2010-05-05
期刊：
影响因子：
29
通讯作者：
Teleman, Aurelio A.
中科院分区：
文献类型：
--
作者：
Hahn, Katrin;Miranda, Merce;Teleman, Aurelio A.
胰岛素/TOR信号通路在动物体内平衡中起着至关重要的作用，通过感知营养状态来调节机体的生长和代谢。我们在这里确定了果蝇B的PP2A调控亚基（PP2A-B）作为胰岛素途径的一个新的、保守的组成部分，它特异性地靶向PP2A全酶使S6K去磷酸化。PP2A-B基因敲除果蝇的S6K磷酸化水平升高，并表现出胰岛素信号升高的典型表型，如降低全身甘油三酯和缩短寿命。我们发现PP2A-B'在物理上和遗传上都与S6K相互作用。PP2A-B'的人类同源物PPP2R5C也能抵消S6K1磷酸化，表明其在哺乳动物中具有保守机制。由于S6K影响癌症和代谢性疾病的发展，我们的数据确定PPP2R5C是一个潜在的医学相关性的新因素。
The insulin/TOR signaling pathway plays a crucial role in animal homeostasis, sensing nutrient status to regulate organismal growth and metabolism. We identify here the Drosophila B' regulatory subunit of PP2A (PP2A-B') as a novel, conserved component of the insulin pathway that specifically targets the PP2A holoenzyme to dephosphorylate S6K. PP2A-B' knockout flies have elevated S6K phosphorylation and exhibit phenotypes typical of elevated insulin signaling such as reduced total body triglycerides and reduced longevity. We show that PP2A-B' interacts with S6K both physically and genetically. The human homolog of PP2A-B', PPP2R5C, also counteracts S6K1 phosphorylation, indicating a conserved mechanism in mammals. Since S6K affects development of cancer and metabolic disease, our data identify PPP2R5C as a novel factor of potential medical relevance.