An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling.

An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling.
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DOI:
10.1083/jcb.134.5.1283
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发表时间:
1996-09
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Peifer M
Peifer M
中科院分区:
其他
文献类型:
--
作者:
Orsulic S;Peifer M

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犰狳是脊椎动物β-连环蛋白的果蝇同源物,在无翼信号传导和粘附连接的组装中发挥着关键作用。我们通过在整个动物的背景下生成和检查一系列犰狳突变体,对粘附连接蛋白进行了首次体内结构功能研究。我们通过测定每个突变体的生物学功能、其结合通常与粘附连接中的犰狳相关的蛋白质的能力、其细胞定位及其磷酸化模式来测试每个突变体。我们绘制了 DE-钙粘蛋白和 α-连环蛋白的结合位点。尽管它们彼此独立地与犰狳结合,但每个结合对于粘附连接的功能都是必需的。我们确定了犰狳的两个独立区域对于无翼信号传导至关重要。我们证明了内源性犰狳在细胞核中积累,并提供了证据表明它可能在细胞核中传导 Wingless 信号。我们发现,构成犰狳中央三分之二的手臂重复序列在不同过程中的功能重要性有所不同。最后,我们证明了犰狳在粘附连接和 Wingless 信号传导中的作用是独立的。我们讨论了犰狳在每个过程中的潜在生化作用。
Armadillo, the Drosophila homologue of vertebrate beta-catenin, plays a pivotal role both in Wingless signaling and in assembly of adherens junctions. We performed the first in vivo structure-function study of an adherens junction protein, by generating and examining a series of Armadillo mutants in the context of the entire animal. We tested each mutant by assaying its biological function, its ability to bind proteins that normally associate with Armadillo in adherens junctions, its cellular localization, and its pattern of phosphorylation. We mapped the binding sites for DE-cadherin and alpha-catenin. Although these bind to Armadillo independently of each other, binding of each is required for the function of adherens junctions. We identified two separate regions of Armadillo critical for Wingless signaling. We demonstrated that endogenous Armadillo accumulates in the nucleus and provide evidence that it may act there in transducing Wingless signal. We found that the Arm repeats, which make up the central two-thirds of Armadillo, differ among themselves in their functional importance in different processes. Finally, we demonstrated that Armadillo's roles in adherens junctions and Wingless signaling are independent. We discuss the potential biochemical role of Armadillo in each process.