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首页> 外文期刊>The FEBS journal >Serum- and glucocorticoid-dependent kinase-1-induced cell migration is dependent on vinculin and regulated by the membrane androgen receptor
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Serum- and glucocorticoid-dependent kinase-1-induced cell migration is dependent on vinculin and regulated by the membrane androgen receptor

机译：血清和糖皮质激素依赖性激酶-1诱导的细胞迁移取决于纽蛋白，并受膜雄激素受体调节

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The serum- and glucocorticoid-dependent kinases 13 (SGK13) are downstream effectors of phosphatidylinositol 3-kinases, implicated in various cell responses including colon cancer tumorigenesis in mice. Here, we investigated the role of SGK1 in the regulation of cell motility. Using Caco-2 colon tumor and HEK293 embryonic kidney cells, we report that transfection with the constitutively active SGK1 mutant (SGK1-SD) significantly enhanced cell motility. The cell-adhesion protein vinculin was effectively dephosphorylated in SGK1-SD-transfected cells. Treatment of the cells with phosphatase inhibitors restored vinculin phosphorylation and inhibited cell migration, indicating a significant role for vinculin phosphorylation in SGK1-induced motility. SGK1-SD-enhanced cell motility was inhibited by activation of membrane androgen-binding sites (mAR) via testosterone-conjugates in both cell lines, whereas intracellular androgen receptor (iAR)-silencing and flutamide treatment revealed that these effects were clearly independent of the interaction of SGK1 with the classical androgen receptors (iAR). More importantly, mAR activation restored vinculin phosphorylation in SGK1-SD-transfected cells, whereas silencing of vinculin fully reversed the mAR-induced inhibition of the migratory capacity, implying that this protein is directly involved in cell motility regulation by SGK1 and mAR. This study indicates for the first time that SGK1 regulates cell migration via vinculin dephosphorylation, a mechanism that is controlled by mAR function.
机译：血清和糖皮质激素依赖性激酶13（SGK13）是磷脂酰肌醇3激酶的下游效应物，参与小鼠的各种细胞反应，包括结肠癌的肿瘤发生。在这里，我们研究了SGK1在调节细胞运动中的作用。使用Caco-2结肠肿瘤和HEK293胚胎肾细胞，我们报道用组成型活性SGK1突变体（SGK1-SD）转染显着增强了细胞运动性。在SGK1-SD转染的细胞中，细胞粘附蛋白纽蛋白被有效地去磷酸化。用磷酸酶抑制剂处理细胞恢复了纽蛋白磷酸化并抑制了细胞迁移，表明纽蛋白磷酸化在SGK1诱导的运动中具有重要作用。 SGK1-SD增强的细胞运动被两种细胞系中经由睾丸激素结合物的膜雄激素结合位点（mAR）激活所抑制，而细胞内雄激素受体（iAR）沉默和氟他胺治疗表明这些作用明显独立于SGK1与经典雄激素受体（iAR）的相互作用。更重要的是，mAR激活可恢复SGK1-SD转染的细胞中的纽蛋白磷酸化，而纽蛋白的沉默则完全逆转了mAR诱导的对迁移能力的抑制作用，这表明该蛋白直接参与SGK1和mAR的细胞运动性调节。这项研究首次表明SGK1通过纽蛋白脱磷酸作用来调节细胞迁移，该功能受mAR功能控制。

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