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首页> 外文期刊>Oncogene >Levels of PTEN protein modulate Akt phosphorylation on serine 473, but not on threonine 308, in IGF-II-overexpressing rhabdomyosarcomas cells
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Levels of PTEN protein modulate Akt phosphorylation on serine 473, but not on threonine 308, in IGF-II-overexpressing rhabdomyosarcomas cells

机译：在过表达IGF-II的横纹肌肉瘤细胞中，PTEN蛋白的水平调节丝氨酸473而不是苏氨酸308的Akt磷酸化

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Constitutive activation of Akt has been found in many types of human cancer, and is believed to promote proliferation and increased cell survival thereby contributing to cancer progression. In this study, we examined Akt phosphorylation on Ser473 and Thr308 in seven IGF-II-overexpressing rhabdomyosarcomas (RMS) cells. All the RMS cell lines tested had high levels of Akt phosphorylation on Thr308, whereas three cell lines (Rh5, Rh18, and CTR) had a much lower level of Akt phosphorylation on Ser473. To determine whether the difference in Akt phosphorylation on Ser473, but not on Thr308, observed among cell lines is a cell-specific phenomenon or due to other factors, which possibly downregulate Akt phosphorylation, we examined expression of PTEN protein, which acts as a negative regulator of the PI3K/Akt signaling pathway through its ability to dephosphorylate phosphatidylinositol 3,4,5-triphosphate (PIP3). The levels of PTEN expression inversely correlate with Akt phosphorylation on Ser473, but not on Thr308. Consistent with this finding, transfection of wild-type PTEN into RMS and mouse myoblast C2C12 cells resulted in reduced Akt phosphorylation on Ser473, but not on Thr308. Our data suggest that Ser473 may be a key target residue for PTEN to modulate the effects of IGF-II on activating the PI3K/Akt pathway in RMS cells. A better understanding of the pathway in RMS will likely contribute to insights into the biology of the RMS tumorigenesis and hopefully lead to novel therapeutic options.
机译：在许多类型的人类癌症中都发现了Akt的组成型激活，据信它可以促进增殖和增加细胞存活率，从而有助于癌症的发展。在这项研究中，我们检查了7个过表达IGF-II的横纹肌肉瘤（RMS）细胞中Ser473和Thr308的Akt磷酸化。所有测试的RMS细胞系在Thr308上具有高水平的Akt磷酸化，而三种细胞系（Rh5，Rh18和CTR）在Ser473上具有低得多的Akt磷酸化。为了确定在细胞系中观察到的Ser473而不是Thr308的Akt磷酸化差异是细胞特异性现象还是由于其他可能下调Akt磷酸化的因素所致，我们检查了PTEN蛋白的表达，该蛋白为阴性PI3K / Akt信号通路的调节剂通过其使磷脂酰肌醇3,4,5-三磷酸（PIP3）脱磷酸的能力来调节。 PTEN表达水平与Ser473而不是Thr308的Akt磷酸化呈负相关。与该发现一致的是，将野生型PTEN转染到RMS和小鼠成肌细胞C2C12细胞中导致Ser473而不是Thr308的Akt磷酸化降低。我们的数据表明，Ser473可能是PTEN调节IGF-II激活RMS细胞中PI3K / Akt途径的作用的关键靶标残基。对RMS途径的更好理解可能会有助于深入了解RMS肿瘤发生的生物学，并有望带来新的治疗选择。

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