Association between a transmembrane protein tyrosine phosphatase and the cadherin-catenin complex.
Association between a transmembrane protein tyrosine phosphatase and the cadherin-catenin complex.
复制标题
跨膜蛋白酪氨酸磷酸酶与钙粘蛋白-连环蛋白复合物之间的关联。
DOI：
10.1083/jcb.134.6.1519
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发表时间：
1996-09
影响因子：
7.8
通讯作者：
Reichardt, L F
中科院分区：
文献类型：
--
作者：
Kypta, R M;Su, H;Reichardt, L F
钙粘蛋白是钙依赖性细胞粘附分子，在胚胎发育、组织形态发生和癌症中发挥重要作用。其功能的先决条件是通过连环蛋白与肌动蛋白细胞骨架结合。β-连环蛋白的酪氨酸磷酸化与钙粘蛋白依赖性细胞粘附的减少相关，可能为细胞提供调节钙粘蛋白活性的机制。在这里，我们报告，β-连环蛋白免疫沉淀物从PC 12细胞含有酪氨酸磷酸酶活性，脱磷酸化β-连环蛋白在体外。此外，我们发现，白细胞抗原相关蛋白（LAR）相关的跨膜酪氨酸磷酸酶家族（LAR-PTP）的成员与钙粘蛋白-连环蛋白复合物。这种结合需要β-连环蛋白的氨基末端结构域，但不需要介导与钙粘蛋白结合的犰狳重复序列。在缺乏α-连环蛋白的PC 9细胞中也检测到这种相互作用。因此，这种结合不是由α-连环蛋白或钙粘蛋白介导的。有趣的是，LAR-PTP以TrkA依赖的方式在酪氨酸上磷酸化，并且它们与钙粘蛋白-连环蛋白复合物的结合在用NGF处理的细胞中减少。我们认为，在神经突生长过程中，TrkA和LAR-PTP介导的β-连环蛋白酪氨酸磷酸化的变化控制钙粘蛋白的粘附功能。
Cadherins are calcium-dependent cell adhesion molecules that play fundamental roles in embryonic development, tissue morphogenesis, and cancer. A prerequisite for their function is association with the actin cytoskeleton via the catenins. Tyrosine phosphorylation of beta- catenin, which correlates with a reduction in cadherin-dependent cell adhesion, may provide cells with a mechanism to regulate cadherin activity. Here we report that beta-catenin immune precipitates from PC12 cells contain tyrosine phosphatase activity which dephosphorylates beta-catenin in vitro. In addition, we show that a member of the leukocyte antigen-related protein (LAR)-related transmembrane tyrosine phosphatase family (LAR-PTP) associates with the cadherin-catenin complex. This association required the amino-terminal domain of beta- catenin but does not require the armadillo repeats, which mediate association with cadherins. The interaction also is detected in PC9 cells, which lack alpha-catenin. Thus, the association is not mediated by alpha-catenin or by cadherins. Interestingly, LAR-PTPs are phosphorylated on tyrosine in a TrkA-dependent manner, and their association with the cadherin-catenin complex is reduced in cells treated with NGF. We propose that changes in tyrosine phosphorylation of beta-catenin mediated by TrkA and LAR-PTPs control cadherin adhesive function during processes such as neurite outgrowth.