A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth
A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth
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DOI：
10.1038/sj.onc.1210175
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发表时间：
2007-06-07
期刊：
影响因子：
8
通讯作者：
Vogt, P. K.
中科院分区：
文献类型：
--
作者：
Denning, G.;Jean-Joseph, B.;Vogt, P. K.
10号染色体上缺失的磷酸酶和张力蛋白同源物（Phosphatase and tensin homolog deleted on chromosome 10，PTEN）是一种重要的细胞生长负调控因子和肿瘤抑制因子。其生长衰减活性基于磷脂酰肌醇3，4，5-三磷酸（PIP 3）的去磷酸化，PIP 3是磷酸肌醇3-激酶/Akt信号传导途径的必需第二信使。这种活性可能需要定位的PTEN细胞质膜。然而，PTEN也可以定位于细胞核，其功能尚不清楚。在这里，我们提出的数据，德。在PTEN的N-末端区域中有一个短序列，是细胞质定位所必需的。我们将该序列称为细胞质定位信号（CLS）。它可以作为一个非典型信号的核输出或作为一个细胞质滞留信号的PTEN。CLS内的突变诱导核定位并损害PTEN的生长抑制活性，同时保留脂质磷酸酶活性。我们提出，核定位的PTEN是不兼容的质膜靶向生长抑制功能的PTEN。
Phosphatase and tensin homolog deleted on chromosome 10 ( PTEN) is an important negative regulator of cell growth and a tumor suppressor. Its growth-attenuating activity is based on the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate ( PIP3), an essential second messenger for the phosphoinositide 3-kinase/Akt signaling pathway. This activity may require localization of PTEN to cytoplasmic membranes. Yet PTEN can also localize to the cell nucleus where its functions remain unclear. Here we present data that de. ne a short sequence in the N-terminal region of PTEN required for cytoplasmic localization. We will refer to this sequence as cytoplasmic localization signal ( CLS). It could function as a non-canonical signal for nuclear export or as a cytoplasmic retention signal of PTEN. Mutations within the CLS induce nuclear localization and impair growth suppressive activities of PTEN while preserving lipid phosphatase activity. We propose that nuclear localization of PTEN is not compatible with plasma membrane-targeted growth suppressive functions of PTEN.