p120ctn binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity
p120ctn binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity
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DOI：
10.1074/jbc.274.30.21409
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发表时间：
1999-07-23
影响因子：
4.8
通讯作者：
Ozawa, M
中科院分区：
文献类型：
--
作者：
Ohkubo, T;Ozawa, M
钙粘蛋白是一种跨膜糖蛋白，参与Ca 2+依赖的细胞间粘附。以前，我们表明，保守的E钙粘蛋白细胞质结构域的近膜区域负调节粘附活性。在这份报告中，我们提供了几条证据表明p120（ctn）参与了这种负调控。p120（ctn）与无功能羧基端缺失的E-钙粘蛋白的近膜区结合。在该区域的一个额外的内部缺失阻止了与p120（ctn）的关联，并激活了蛋白质，如在聚集测定中所见。此外，无功能的E-钙粘蛋白可以通过共表达p120（ctn）蛋白与氨基末端缺失，消除几个潜在的丝氨酸/苏氨酸磷酸化位点，但不影响结合钙粘蛋白的能力，最后，我们表明，星形孢菌素，激酶抑制剂，诱导增加电泳迁移率的p120（ctn）结合E-钙粘蛋白多肽，激活非功能性E-钙粘蛋白，并将野生型E-钙粘蛋白和E-钙粘蛋白-α-连环蛋白嵌合蛋白从细胞松弛素D敏感状态转化为细胞松弛素D不敏感状态。总之，这些结果表明，p120（ctn）是一种调节剂的E-钙粘蛋白介导的细胞粘附。
Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Previously, we showed that the conserved membrane-proximal region of the E cadherin cytoplasmic domain negatively regulates adhesion activity. In this report, we provide several lines of evidence that p120(ctn) is involved in this negative regulation. p120(ctn) binds to the membrane-proximal region of the nonfunctional carboxyl-terminally deleted E-cadherin protein. An additional internal deletion in this region prevented the association with p120(ctn) and activated the protein, as seen in an aggregation assay. Furthermore, the nonfunctional E-cadherin can be activated through coexpression of p120(ctn) proteins with amino-terminal deletions, which eliminate several potential serine/threonine phosphorylation sites but do not affect the ability to bind to cadherins, Finally, we show that staurosporine, a kinase inhibitor, induces an increased electrophoretic mobility of p120(ctn) bound to E-cadherin polypeptides, activates the nonfunctional E-cadherin protein, and converts the wildtype E-cadherin and an E-cadherin-alpha-catenin chimeric protein from a cytochalasin D-sensitive to a cytochalasin D-insensitive state. Together, these results indicate that p120(ctn) is a modulator of E-cadherin-mediated cell adhesion.