Phosphorylation and free pool of β-catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration
Phosphorylation and free pool of β-catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration
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DOI：
10.1074/jbc.274.15.10173
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发表时间：
1999-04-09
影响因子：
4.8
通讯作者：
Ullrich, A
中科院分区：
文献类型：
--
作者：
Müller, T;Choidas, A;Ullrich, A
细胞迁移需要精确的控制，当肿瘤细胞变得侵袭和转移时，这种控制就会改变或丢失。尽管细胞与细胞接触的完整性（例如粘附连接）对于维持功能性上皮细胞至关重要，但它们在迁移过程中需要快速分解。跨膜细胞粘附蛋白 E-钙粘蛋白和细胞质连环蛋白是这些结构的分子元件。在这里，我们证明上皮细胞迁移伴随着β-连环蛋白的酪氨酸磷酸化及其游离细胞质库的增加。我们进一步表明，蛋白酪氨酸磷酸酶 LAR（白细胞共同抗原相关）与上皮细胞中的钙粘蛋白-连环蛋白复合物共定位，并与 β-连环蛋白和斑珠蛋白相关。有趣的是，蛋白酪氨酸磷酸酶 (PTP) LAR 的异位表达通过阻止磷酸化和 β-连环蛋白自由池的增加来抑制上皮细胞迁移；此外，它还能抑制裸鼠肿瘤的形成。这些数据支持 PTP LAR 在粘附连接处上皮细胞-细胞接触的调节以及 β-连环蛋白信号传导功能的控制中的功能。因此，PTP-LAR似乎在维持上皮完整性中发挥着重要作用，其调节功能的丧失可能导致恶性进展和转移。
Cell migration requires precise control, which is altered or lost when tumor cells become invasive and metastatic, Although the integrity of cell-cell contacts, such as adherens junctions, is essential for the maintenance of functional epithelia, they need to be rapidly disassembled during migration. The transmembrane cell adhesion protein E-cadherin and the cytoplasmic catenins are molecular elements of these structures. Here we demonstrate that epithelial cell migration is accompanied by tyrosine phosphorylation of beta-catenin and an increase of its free cytoplasmic pool. We show further that the protein-tyrosine phosphatase LAR (leukocyte common antigen related) colocalizes with the cadherin-catenin complex in epithelial cells and associates with beta-catenin and plakoglobin, Interestingly, ectopic expression of protein-tyrosine phosphatase (PTP) LAR inhibits epithelial cell migration by preventing phosphorylation and the increase in the free pool of beta-catenin; moreover, it inhibits tumor formation in nude mice. These data support a function for PTP LAR in the regulation of epithelial cell-cell contacts at adherens junctions as well as in the control of beta-catenin signaling functions. Thus PTP-LAR appears to play an important role in the maintenance of epithelial integrity, and a loss of its regulatory function may contribute to malignant progression and metastasis.