Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin.

Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin.
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DOI:
10.1083/jcb.124.5.729
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发表时间:
1994-03
影响因子:
7.8
通讯作者:
Papkoff, J
Papkoff, J
中科院分区:
生物学1区
文献类型:
--
作者:
Hinck, L;Nelson, W J;Papkoff, J

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Wnt-1同源物已在无脊椎动物和脊椎动物中被鉴定,并且在细胞分化和组织中起重要作用。在果蝇中,片段极性基因wingless(Wnt-1同源物)和犰狳的产物参与胚胎发育中细胞边界形成的重要信号转导途径,但蛋白质之间的功能相互作用尚不清楚。我们研究了哺乳动物细胞中Wnt-1的功能,已知犰狳(β-连环蛋白和斑珠蛋白)可以结合并调节钙粘蛋白细胞粘附蛋白。我们发现Wnt-1表达导致β-连环蛋白和斑珠蛋白的积累。此外,β-连环蛋白与细胞粘附蛋白钙粘蛋白的结合是稳定的,导致钙依赖性细胞-细胞粘附强度的伴随增加。因此,Wnt-1和犰狳家族成员之间的功能相互作用的结果是细胞-细胞粘附的加强,这可能导致细胞边界的规范。
Wnt-1 homologs have been identified in invertebrates and vertebrates and play important roles in cellular differentiation and organization. In Drosophila, the products of the segment polarity genes wingless (the Wnt-1 homolog) and armadillo participate in a signal transduction pathway important for cellular boundary formation in embryonic development, but functional interactions between the proteins are unknown. We have examined Wnt-1 function in mammalian cells in which armadillo (beta-catenin and plakoglobin) is known to bind to and regulate cadherin cell adhesion proteins. We show that Wnt-1 expression results in the accumulation of beta-catenin and plakoglobin. In addition, binding of beta-catenin to the cell adhesion protein, cadherin, is stabilized, resulting in a concomitant increase in the strength of calcium-dependent cell-cell adhesion. Thus, a consequence of the functional interaction between Wnt-1 and armadillo family members is the strengthening of cell-cell adhesion, which may lead to the specification of cellular boundaries.