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首页> 外文期刊>Cell metabolism >P70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake
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P70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake

机译：P70S6激酶使丝氨酸491上的AMPK磷酸化，以调节瘦素对食物摄入的影响

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摘要

The PI3K-AKT, mTOR-p70S6 kinase and AMPK pathways play distinct and critical roles in metabolic regulation. Each pathway is necessary for leptin's anorexigenic effects in the hypothalamus. Here we show that these pathways converge in an integrated phosphorylation cascade to mediate leptin action in the hypothalamus. We identify serine 491 on α2AMPK as the site of convergence and show that p70S6 kinase forms a complex with α2AMPK, resulting in phosphorylation on serine 491. Blocking α2AMPK-serine 491 phosphorylation increases hypothalamic AMPK activity, food intake, and body weight. Serine 491 phosphorylation is necessary for leptin's effects on hypothalamic α2AMPK activity, neuropeptide expression, food intake, and body weight. These results identify an inhibitory AMPK kinase, p70S6 kinase, and demonstrate that AMPK is a substrate for mTOR-p70S6 kinase. This discovery has broad biologic implications since mTOR-p70S6 kinase and AMPK have multiple, fundamental and generally opposing cellular effects that regulate metabolism, cell growth, and development.
机译：PI3K-AKT，mTOR-p70S6激酶和AMPK途径在代谢调节中起着独特而关键的作用。每个途径对于瘦素在下丘脑中的厌食作用都是必需的。在这里，我们显示这些通路在整合的磷酸化级联中汇聚，以调节下丘脑中的瘦素作用。我们将α2AMPK上的丝氨酸491确定为收敛位点，并显示p70S6激酶与α2AMPK形成复合物，导致丝氨酸491上的磷酸化。阻断α2AMPK-丝氨酸491的磷酸化可增加下丘脑AMPK活性，食物摄入和体重。丝氨酸491的磷酸化对于瘦素对下丘脑α2AMPK活性，神经肽表达，食物摄入和体重的影响是必需的。这些结果确定了抑制性的AMPK激酶p70S6激酶，并证明AMPK是mTOR-p70S6激酶的底物。该发现具有广泛的生物学意义，因为mTOR-p70S6激酶和AMPK具有调控新陈代谢，细胞生长和发育的多种，基本且普遍相反的细胞作用。

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