The Phosphatase PTP-PEST/PTPN12 Regulates Endothelial Cell Migration and Adhesion, but Not Permeability, and Controls Vascular Development and Embryonic Viability*
The Phosphatase PTP-PEST/PTPN12 Regulates Endothelial Cell Migration and Adhesion, but Not Permeability, and Controls Vascular Development and Embryonic Viability*
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DOI：
10.1074/jbc.m112.387456
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发表时间：
2012-10
期刊：
影响因子：
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通讯作者：
C. M. Souza;Dominique Davidson;Inmoo Rhee;J. Gratton;E. Davis;A. Veillette
中科院分区：
文献类型：
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作者：
C. M. Souza;Dominique Davidson;Inmoo Rhee;J. Gratton;E. Davis;A. Veillette
背景：PTP-PEST是一种对胚胎存活至关重要的磷酸酶。结果：PTP-PEST对内皮细胞的粘附和迁移至关重要。其在内皮细胞中的缺失导致小鼠胚胎死亡。结论：组成型PTP-PEST缺陷小鼠的胚胎活力是由于内皮细胞功能缺陷。意义：PTP-PEST是体外和体内内皮细胞功能的关键调节剂。蛋白酪氨酸磷酸酶（PTP）-PEST（PTPN 12）广泛表达。它对小鼠的正常胚胎发育和胚胎活力至关重要。在这里，我们解决了PTP-PEST参与内皮细胞功能的遗传和生物化学的方法相结合。通过从诱导型PTP-PEST缺陷小鼠产生原代内皮细胞，我们发现PTP-PEST对于内皮细胞分化和增殖或对于内皮细胞通透性的控制是不需要的。然而，它是整合素介导的内皮细胞粘附和迁移所必需的。PTP-PEST缺陷型内皮细胞显示Cas、桩蛋白和Pyk 2的酪氨酸磷酸化增加，这些蛋白以前也与整合素功能有关。通过在体内消除内皮细胞中的PTP-PEST，我们获得了PTP-PEST在内皮细胞中的表达是正常血管发育和胚胎存活所必需的证据。因此，PTP-PEST是内皮细胞中整合素介导的功能的关键调节剂，似乎是通过其控制Cas、桩蛋白和Pyk 2的能力。这一功能至少部分解释了PTP-PEST在胚胎发育和生存能力中的重要作用。
Background: PTP-PEST is a phosphatase essential for embryonic viability. Results: PTP-PEST is critical for adhesion and migration of endothelial cells. Its absence in endothelial cells results in mouse embryonic lethality. Conclusion: The embryonic viability seen in constitutive PTP-PEST-deficient mice is due to a defect in endothelial cell functions. Significance: PTP-PEST is a key regulator of endothelial cell functions in vitro and in vivo. Protein-tyrosine phosphatase (PTP)-PEST (PTPN12) is ubiquitously expressed. It is essential for normal embryonic development and embryonic viability in mice. Herein we addressed the involvement of PTP-PEST in endothelial cell functions using a combination of genetic and biochemical approaches. By generating primary endothelial cells from an inducible PTP-PEST-deficient mouse, we found that PTP-PEST is not needed for endothelial cell differentiation and proliferation or for the control of endothelial cell permeability. Nevertheless, it is required for integrin-mediated adhesion and migration of endothelial cells. PTP-PEST-deficient endothelial cells displayed increased tyrosine phosphorylation of Cas, paxillin, and Pyk2, which were previously also implicated in integrin functions. By eliminating PTP-PEST in endothelial cells in vivo, we obtained evidence that expression of PTP-PEST in endothelial cells is required for normal vascular development and embryonic viability. Therefore, PTP-PEST is a key regulator of integrin-mediated functions in endothelial cells seemingly through its capacity to control Cas, paxillin, and Pyk2. This function explains at least in part the essential role of PTP-PEST in embryonic development and viability.