Interaction of Gα12 and Gα13 with the cytoplasmic domain of cadherin provides a mechanism for β-catenin release
Interaction of Gα12 and Gα13 with the cytoplasmic domain of cadherin provides a mechanism for β-catenin release
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DOI：
10.1073/pnas.021350998
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发表时间：
2001-01-16
影响因子：
11.1
通讯作者：
Casey, PJ
中科院分区：
文献类型：
--
作者：
Meigs, TE;Fields, TA;Casey, PJ
异源三聚体 G 蛋白的 G11 亚家族由 α 亚基 G α 12 和 G α 13 组成，已被认为是从细胞骨架变化到细胞生长和肿瘤发生等细胞过程中的信号传导成分。为了阐明该亚家族在细胞调节中的特定作用，我们试图确定 G α 12 的分子靶标。在这里，我们展示了 G12 亚家族与细胞表面粘附蛋白钙粘蛋白家族的几个成员的细胞质尾部之间的特定相互作用。 G α 12 或 G α 13 结合导致转录激活剂 β-连环蛋白从钙粘蛋白上解离，此外，在缺乏 β-连环蛋白降解所需的腺瘤性息肉病线圈蛋白的细胞中，突变激活的 G α 12 或 G α 13 的表达导致 β-连环蛋白介导的转录激活增加。这些发现为先前报道的 G12 亚家族的细胞转化能力提供了潜在的分子机制，并揭示了异源三聚体 G 蛋白与控制生长和分化的细胞过程之间的联系。
The G11 subfamily of heterotrimeric G proteins, comprised of the alpha -subunits G alpha 12 and G alpha 13, has been implicated as a signaling component in cellular processes ranging from cytoskeletal changes to cell growth and oncogenesis. In an attempt to elucidate specific roles of this subfamily in cell regulation, we sought to identify molecular targets of G alpha 12, Here we show a specific interaction between the G12 subfamily and the cytoplasmic tails of several members of the cadherin family of cell-surface adhesion proteins. G alpha 12 or G alpha 13 binding causes dissociation of the transcriptional activator beta -catenin from cadherins, Furthermore, in cells lacking the adenomatous polyposis coil protein required for beta -catenin degradation, expression of mutationally activated G alpha 12 or G alpha 13 causes an increase in beta -catenin-mediated transcriptional activation, These findings provide a potential molecular mechanism for the previously reported cellular transforming ability of the G12 subfamily and reveal a link between heterotrimeric G proteins and cellular processes controlling growth and differentiation.