The tumor suppressor PTEN is necessary for human sprouty 2-mediated inhibition of cell proliferation
The tumor suppressor PTEN is necessary for human sprouty 2-mediated inhibition of cell proliferation
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DOI：
10.1074/jbc.m508300200
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发表时间：
2006-02-24
影响因子：
4.8
通讯作者：
Patel, TB
中科院分区：
文献类型：
--
作者：
Edwin, F;Singh, R;Patel, TB
豆芽家族蛋白是生长因子作用的新型调节剂。人Sprouty 2（hSPRY2）抑制许多不同细胞类型的增殖。然而，hSPRY2的抗增殖作用所涉及的机制仍有待阐明。在这里，我们已经证明，hSPRY2增加的数量的肿瘤抑制磷酸酶和张力蛋白同源物10号染色体上删除（PTEN），并减少其磷酸化。由此产生的PTEN活性的增加反映在表皮生长因子和血清对Akt的活化减少。与增加的PTEN活性一致，在表达hSPRY2的细胞中，细胞从G（1）期到S期的进展减少。通过使用PTEN无效的原代小鼠胚胎成纤维细胞和它们的同基因对照以及针对PTEN的小干扰RNA，我们证明了PTEN对于hSPRY2抑制表皮生长因子激活Akt以及细胞增殖是必需的。总之，我们得出结论，hSPRY2通过改变PTEN含量和活性介导其抗增殖作用。
Sprouty family proteins are novel regulators of growth factor actions. Human Sprouty 2 (hSPRY2) inhibits the proliferation of a number of different cell types. However, the mechanisms involved in the anti-proliferative actions of hSPRY2 remain to be elucidated. Here we have demonstrated that hSPRY2 increases the amount of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 ( PTEN) and decreases its phosphorylation. The resultant increase in PTEN activity is reflected in decreased activation of Akt by epidermal growth factor and serum. Consistent with increased PTEN activity, in hSPRY2-expressing cells, the progression of cells from the G(1) to S phase is decreased. By using PTEN null primary mouse embryonic fibroblasts and their isogenic controls as well as small interfering RNA against PTEN, we demonstrated that PTEN is necessary for hSPRY2 to inhibit Akt activation by epidermal growth factor as well as cell proliferation. Overall, we concluded that hSPRY2 mediates its anti-proliferative actions by altering PTEN content and activity.