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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >PTEN as an effector in the signaling of antimigratory G protein-coupled receptor
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PTEN as an effector in the signaling of antimigratory G protein-coupled receptor

机译：PTEN作为抗迁移G蛋白偶联受体信号转导的效应子

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PTEN, a tumor suppressor phosphatase, is important in the regulation of cell migration and invasion. Physiological regulation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) by cell surface receptors has not been described. Here, we show that the bioactive lipid sphingosine 1-phosphate (S1P), which acts through the S1P2 receptor (S1P2R) G protein-coupled receptor (GPCR) to inhibit cell migration, utilizes PTEN as a signaling intermediate. S1P2R inhibition of cell migration is abrogated by dominant-negative PTEN expression. S1P was unable to efficiently inhibit the migration of Pten~(ΔloxP/ΔloxP) mouse embryonic fibro-blasts; however, the antimigratory effect was restored upon the expression of PTEN. S1P2R activation of Rho GTPase is not affected in Pten~(ΔloxP/ΔloxP) cells, and dominant-negative Rho GTPase reversed S1P inhibition of cell migration in WT cells but not in Pten~(ΔloxP/ΔloxP) cells, suggesting that PTEN acts downstream of the Rho GTPase. Ligand activation of the S1P2R receptor stimulated the coimmu-noprecipitation of S1P2R and PTEN. Interestingly, S1P2R signaling increased PTEN phosphatase activity in membrane fractions. Furthermore, tyrosine phosphorylation of PTEN was stimulated by S1P2R signaling. These data suggest that the S1P2R receptor actively regulates the PTEN phosphatase by a Rho GTPase-depen-dent pathway to inhibit cell migration. GPCR regulation of PTEN maybe a general mechanism in signaling events of cell migration and invasion.
机译：PTEN是一种肿瘤抑制磷酸酶，在调节细胞迁移和侵袭中很重要。尚未描述细胞表面受体对PTEN（在10号染色体上缺失的磷酸酶和张力蛋白同源物）的生理调节。在这里，我们显示生物活性脂质鞘氨醇1-磷酸（S1P）通过S1P2受体（S1P2R）G蛋白偶联受体（GPCR）来抑制细胞迁移，并利用PTEN作为信号传导中间体。 S1P2R对细胞迁移的抑制被显性阴性PTEN表达消除。 S1P不能有效抑制Pten〜（ΔloxP/ΔloxP）小鼠胚胎成纤维细胞的迁移。然而，抗迁移作用在PTEN表达后得以恢复。 Rho GTPase的S1P2R激活在Pten〜（ΔloxP/ΔloxP）细胞中不受影响，显性负性Rho GTPase逆转WT细胞中S1P对细胞迁移的抑制，但在Pten〜（ΔloxP/ΔloxP）细胞中没有，表明PTEN在下游起作用Rho GTPase。 S1P2R受体的配体激活刺激了S1P2R和PTEN的共沉淀。有趣的是，S1P2R信号传导增加了膜级分中的PTEN磷酸酶活性。此外，PTEN的酪氨酸磷酸化受到S1P2R信号的刺激。这些数据表明，S1P2R受体通过Rho GTPase依赖性途径主动调节PTEN磷酸酶，从而抑制细胞迁移。 PTEN的GPCR调节可能是细胞迁移和侵袭信号传递中的一般机制。

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