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一种与连接斑相关的新犰狳家族成员p0071的克隆与特性分析:密切相关蛋白质亚家族的证据

Cloning and characterization of a new armadillo family member, p0071, associated with the junctional plaque: evidence for a subfamily of closely related proteins.

作者信息

Hatzfeld M, Nachtsheim C

机构信息

Max-Planck-Institute for Biophysical Chemistry, Department of Biochemistry, Göttingen, FRG.

出版信息

J Cell Sci. 1996 Nov;109 ( Pt 11):2767-78. doi: 10.1242/jcs.109.11.2767.

Abstract

Cell contacts of the adherens type are organized around transmembrane proteins of the cadherin family. Whereas the extracellular domains mediate homophilic interactions between cadherins of neighbouring cells the cytoplasmic domains organize a set of proteins into the junctional plaque. Among these junctional plaque proteins are members of the armadillo gene family, beta-catenin, plakoglobin (gamma-catenin), B6P/plakophilin and p120. These proteins are assumed to play a key role in cell cell signalling through intercellular junctions. Here we report cloning of a cDNA encoding a new armadillo family member, p0071, closely related to p120 and B6P/plakophilin and more distantly related to armadillo, plakoglobin, beta-catenin and other members of the gene family. The deduced amino acid sequence encodes a basic protein of 1,211 amino acids with a central armadillo repeat region which is conserved in sequence and organization of its ten individual motifs between p120, B6P/plakophilin and p0071. In contrast the end domains of the three proteins are variable in size and sequence. The RNA coding for p0071 is expressed in all tissues examined. Using antibodies generated against the armadillo repeat region of the protein we show that p0071 is localized at cell-cell borders and is expressed in the desmosomal plaque of some cultured epithelial cells. The protein seems to be an accessory component of the desmosomal plaque as well as of other adhesion plaques and might be involved in regulating junctional plaque organization and cadherin function. Our data provide evidence for a subfamily of armadillo related proteins that share not only structural features but also have in common their localisation in the junctional plaque. We therefore suggest that family members exert similar functions and might be involved in cell signalling through cell contacts.

摘要

黏附型细胞接触是围绕钙黏蛋白家族的跨膜蛋白组织起来的。细胞外结构域介导相邻细胞的钙黏蛋白之间的嗜同性相互作用,而细胞质结构域则将一组蛋白质组织成连接斑。这些连接斑蛋白中有犰狳基因家族的成员、β-连环蛋白、桥粒斑珠蛋白(γ-连环蛋白)、B6P/桥粒斑菲素蛋白和p120。这些蛋白质被认为在通过细胞间连接的细胞-细胞信号传导中起关键作用。在此,我们报告了一个编码新的犰狳家族成员p0071的cDNA的克隆,它与p120和B6P/桥粒斑菲素蛋白密切相关,与犰狳、桥粒斑珠蛋白、β-连环蛋白以及该基因家族的其他成员的关系较远。推导的氨基酸序列编码一个由1211个氨基酸组成的碱性蛋白,其中心有一个犰狳重复区域,该区域在p120、B6P/桥粒斑菲素蛋白和p0071之间的十个独立基序的序列和组织上是保守的。相反,这三种蛋白质的末端结构域在大小和序列上是可变的。编码p0071的RNA在所检测的所有组织中都有表达。使用针对该蛋白的犰狳重复区域产生的抗体,我们表明p0071定位于细胞-细胞边界,并在一些培养的上皮细胞的桥粒斑中表达。该蛋白似乎是桥粒斑以及其他黏附斑的辅助成分,可能参与调节连接斑的组织和钙黏蛋白的功能。我们的数据为犰狳相关蛋白的一个亚家族提供了证据,这些蛋白不仅共享结构特征,而且在连接斑中的定位也相同。因此,我们认为该家族成员发挥相似的功能,可能通过细胞接触参与细胞信号传导。

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