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A role for Galpha12/Galpha13 in p120ctn regulation.

机译:Galpha 12 / Galpha 13在p120ctn调节中的作用。

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The catenin p120 (p120ctn) is an armadillo repeat domain protein that binds to cadherins and has been shown to facilitate strong cell-cell adhesion. We have investigated a possible link between heterotrimeric G proteins and p120ctn, and found that both Galpha12 and Galpha13 can completely and selectively abrogate the p120ctn-induced branching phenotype in different cell types. Consistent with these observations, the expression of Galpha12 or Galpha13 compensates for the reduction of Rho activity induced by p120ctn. On the other hand, p120ctn can be selectively coimmunoprecipitated with Galpha12, and the coimmunoprecipitation was favored by activation of the G protein. A specific interaction between p120ctn and Galpha12Q231L was also observed in in vitro binding experiments. In addition, p120ctn can be immunoprecipitated along with Galpha12Q231L in L cells in absence of E-cadherin. Interestingly, the expression of Galpha12Q231L increases the amount of p120ctn associated with E-cadherin. These findings demonstrate that Galpha12 and p120ctn are binding partners, and they also suggest a role for Galpha12 in regulating p120ctn activity and its interaction with cadherins. We propose that the Galpha12-p120ctn interaction acts as a molecular switch, which regulates cadherin-mediated cell-cell adhesion.
机译:连环蛋白p120(p120ctn)是一种犰狳重复结构域蛋白,可与钙黏着蛋白结合,并已显示出可促进细胞与细胞的牢固粘附。我们已经研究了异源三聚体G蛋白和p120ctn之间的可能联系,并发现Galpha12和Galpha13可以完全和选择性地废除p120ctn诱导的不同细胞类型的分支表型。与这些观察结果一致,Galpha12或Galpha13的表达补偿了p120ctn诱导的Rho活性降低。另一方面,p120ctn可以与Galpha12选择性地共免疫沉淀,而G蛋白的活化有利于共免疫沉淀。在体外结合实验中还观察到了p120ctn和Galpha12Q231L之间的特异性相互作用。另外,p120ctn可以与Galpha12Q231L一起在没有E-钙粘蛋白的情况下在L细胞中进行免疫沉淀。有趣的是,Galpha12Q231L的表达增加了与E-cadherin相关的p120ctn的数量。这些发现表明,Galpha12和p120ctn是结合伴侣,它们还暗示了Galpha12在调节p120ctn活性及其与钙粘蛋白的相互作用中的作用。我们建议,Galpha12-p120ctn相互作用作为一个分子开关,调节钙粘蛋白介导的细胞间粘附。

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