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首页> 外文期刊>Molecular and Cellular Biology >Polycystin-1 Regulates Extracellular Signal-Regulated Kinase-Dependent Phosphorylation of Tuberin To Control Cell Size through mTOR and Its Downstream Effectors S6K and 4EBP1
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Polycystin-1 Regulates Extracellular Signal-Regulated Kinase-Dependent Phosphorylation of Tuberin To Control Cell Size through mTOR and Its Downstream Effectors S6K and 4EBP1

机译：Polycystin-1通过mTOR及其下游效应器S6K和4EBP1调节管蛋白的胞外信号调节激酶依赖性磷酸化，以控制细胞大小

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Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease characterized by bilateral renal cyst formation. Both hyperproliferation and hypertrophy have been previously observed in ADPKD kidneys. Polycystin-1 (PC-1), a large orphan receptor encoded by the PKD1 gene and mutated in 85% of all cases, is able to inhibit proliferation and apoptosis. Here we show that overexpression of PC-1 in renal epithelial cells inhibits cell growth (size) in a cell cycle-independent manner due to the downregulation of mTOR, S6K1, and 4EBP1. Upregulation of the same pathway leads to increased cell size, as found in mouse embryonic fibroblasts derived from Pkd1?/? mice. We show that PC-1 controls the mTOR pathway in a Tsc2-dependent manner, by inhibiting the extracellular signal-regulated kinase (ERK)-mediated phosphorylation of tuberin in Ser664. We provide a detailed molecular mechanism by which PC-1 can inhibit the mTOR pathway and regulate cell size.
机译：常染色体显性遗传性多囊肾（ADPKD）是常见的遗传性疾病，其特征是双侧肾囊肿形成。先前已经在ADPKD肾脏中观察到过度增殖和肥大。 Polycystin-1（PC-1）是由 PKD1 基因编码的大型孤儿受体，在所有病例中有85％发生了突变，能够抑制增殖和凋亡。在这里，我们显示由于mTOR，S6K1和4EBP1的下调，肾上皮细胞PC-1的过表达以细胞周期独立的方式抑制了细胞的生长（大小）。如 Pkd1 ？ / ？老鼠。我们显示PC-1通过抑制Ser664中的胞外蛋白的胞外信号调节激酶（ERK）介导的磷酸化，以Tsc2依赖性方式控制mTOR途径。我们提供了PC-1抑制mTOR途径并调节细胞大小的详细分子机制。

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