Regulation of PTEN by Rho small GTPases
Regulation of PTEN by Rho small GTPases
复制标题
DOI：
10.1038/ncb1236
复制
发表时间：
2005-04-01
影响因子：
21.3
通讯作者：
Wu, DQ
中科院分区：
文献类型：
--
作者：
Li, Z;Dong, XM;Wu, DQ
PTEN（磷酸酶与张力蛋白同源物）是一种既能使蛋白质底物去磷酸化，也能使磷酸肌醇底物去磷酸化的磷酸酶。它在多种人类肿瘤中发生突变，并且在包括细胞迁移（5 - 7）和趋化性（8，9）在内的多种生物学过程中发挥重要作用（1 - 4）。在盘基网柄菌（10，11）和小鼠中性粒细胞（12）中，PTEN的细胞内定位以及可能的活性受趋化因子调节。然而，其调节机制仍然不清楚。在此我们表明，RhoA和Cdc42（小GTP酶Rho家族成员（13 - 16））调节白细胞和人转染胚胎肾细胞中PTEN的细胞内定位。此外，活性RhoA能够刺激人胚胎肾细胞和白细胞中PTEN的磷脂磷酸酶活性，并且这种调节似乎需要RhoA的下游效应物RhoA相关激酶（Rock）。再者，我们已经确定了PTEN上受小GTP酶调节所必需的关键残基，并表明小GTP酶介导的PTEN调节在趋化性调节中具有重要作用。
PTEN ( phosphatase and tensin homologue) is a phosphatase that dephosphorylates both protein and phosphoinositide substrates. It is mutated in a variety of human tumours and has important roles in a diverse range of biological processes(1-4), including cell migration(5-7) and chemotaxis(8,9). PTEN's intracellular localization and presumably activity are regulated by chemoattractants in Dictyostelium(10,11) and mouse neutrophils(12). However, the mechanisms for its regulation remain elusive. Here we show that RhoA and Cdc42, members of the Rho family of small GTPases(13-16), regulate the intracellular localization of PTEN in leukocytes and human transfected embryonic kidney cells. In addition, active RhoA is able to stimulate the phospholipid phosphatase activity of PTEN in human embryonic kidney cells and leukocytes, and this regulation seems to require RhoA's downstream effector, RhoA-associated kinase (Rock). Furthermore, we have identified key residues on PTEN that are required for its regulation by the small GTPase, and show that small GTPase-mediated regulation of PTEN has a significant role in the regulation of chemotaxis.