PtdIns(3,4,5)P(3)-dependent and -independent roles for PTEN in the control of cell migration.
PtdIns(3,4,5)P(3)-dependent and -independent roles for PTEN in the control of cell migration.
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DOI：
10.1016/j.cub.2006.12.026
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发表时间：
2007-01-23
期刊：
影响因子：
9.2
通讯作者：
Weijer, Cornelis J.
中科院分区：
文献类型：
--
作者：
Leslie, Nick R.;Yang, Xuesong;Downes, C. Peter;Weijer, Cornelis J.
磷酸酶和张力蛋白同源物（PTEN）通过其PtdIns（3，4，5）P3脂质磷酸酶活性介导其对增殖、生长、存活和迁移的许多作用，抑制磷酸肌醇3-激酶（PI 3 K）依赖性信号传导途径。PTEN还具有蛋白磷酸酶活性，其作用不太清楚。我们研究了PTEN在控制鸡胚中胚层细胞通过原条进入细胞迁移中的作用。PTEN过表达强烈抑制中胚层细胞通过前原条和中原条进入的上皮-间充质转化（EMT），但不影响位于后原条的细胞的EMT。对EMT的抑制活性完全依赖于通过其C-末端PDZ结合位点靶向PTEN，但可以通过仅具有蛋白磷酸酶活性的PTEN突变体（PTEN G129 E）实现。缺乏PDZ结合位点的PTEN或PTENC 2结构域的表达，或通过特异性抑制剂抑制PI 3 K，不抑制EMT，但导致细胞极性和中胚层细胞定向迁移的丧失。通常缺乏任何可检测的脂质和蛋白磷酸酶活性的PTEN相关蛋白TPTE可以通过突变重新激活，并且只有这种重新激活的突变体导致这些细胞在体内的非定向迁移。PTEN通过至少两种不同的机制调节鸡胚中胚层细胞的细胞迁移：控制EMT，这涉及其蛋白磷酸酶活性;和通过其脂质磷酸酶活性控制中胚层细胞的定向运动。
Phosphatase and tensin homolog (PTEN) mediates many of its effects on proliferation, growth, survival, and migration through its PtdIns(3,4,5)P3 lipid phosphatase activity, suppressing phosphoinositide 3-kinase (PI3K)-dependent signaling pathways. PTEN also possesses a protein phosphatase activity, the role of which is less well characterized. We have investigated the role of PTEN in the control of cell migration of mesoderm cells ingressing through the primitive streak in the chick embryo. Overexpression of PTEN strongly inhibits the epithelial-to-mesenchymal transition (EMT) of mesoderm cells ingressing through the anterior and middle primitive streak, but it does not affect EMT of cells located in the posterior streak. The inhibitory activity on EMT is completely dependent on targeting PTEN through its C-terminal PDZ binding site, but can be achieved by a PTEN mutant (PTEN G129E) with only protein phosphatase activity. Expression either of PTEN lacking the PDZ binding site or of the PTEN C2 domain, or inhibition of PI3K through specific inhibitors, does not inhibit EMT, but results in a loss of both cell polarity and directional migration of mesoderm cells. The PTEN-related protein TPTE, which normally lacks any detectable lipid and protein phosphatase activity, can be reactivated through mutation, and only this reactivated mutant leads to nondirectional migration of these cells in vivo. PTEN modulates cell migration of mesoderm cells in the chick embryo through at least two distinct mechanisms: controlling EMT, which involves its protein phosphatase activity; and controlling the directional motility of mesoderm cells, through its lipid phosphatase activity.
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影响因子：
56.9
作者：
Raftopoulou, M;Etienne-Manneville, S;Hall, A
通讯作者：
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影响因子：
9.2
作者：
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作者：
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影响因子：
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作者：
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Mañes, S
DOI：
10.1073/pnas.0409784102
发表时间：
2005-03-22
影响因子：
11.1
作者：
Sanchez, T;Thangada, S;Hla, T
通讯作者：
Hla, T