Retention of membrane-localized β-catenin in cells lacking functional polycystin-1 and tuberin
Retention of membrane-localized β-catenin in cells lacking functional polycystin-1 and tuberin
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DOI：
10.1002/mc.10034
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发表时间：
2002-03-01
影响因子：
4.6
通讯作者：
Walker, CL
中科院分区：
文献类型：
--
作者：
Kugoh, H;Kleymenova, E;Walker, CL
结节性硬化症（TSC）2肿瘤抑制基因编码蛋白质tuberin，其最近被证明在多囊蛋白-1（多囊肾病（PDK）1基因的产物）的细胞内运输中起关键作用。PKD 1是常染色体显性多囊肾病的主要病因，常染色体显性多囊肾病被称为“伪装的肿瘤”。“多囊蛋白-1是一种膜蛋白，定位于含有E-钙粘蛋白和α-、β-和γ-连环蛋白的复合物中的粘附连接处。为了确定多囊蛋白-1和E-钙粘蛋白的膜定位的丧失是否影响β-连环蛋白的功能，β-连环蛋白的定位和信号转导分别在来自多囊、肿瘤和正常大鼠肾上皮细胞的结核菌素缺失的EKT 2和ERC 15细胞以及结核菌素阳性的TRKE 2细胞中进行表征。由于Tsc 2基因失活，缺乏tuberin的EKT 2细胞不能将多囊蛋白-1和E-cadherin适当地定位于这些连接处。然而，β-连环蛋白被保留在侧细胞膜在tuberin无效和tuberin阳性细胞。此外，由β-连环蛋白T细胞特异性转录因子复合物介导的基因转录在EKT 2、ERC 15和TRKE 2细胞中没有差异。因此，β-连环蛋白被稳定地保留在侧细胞膜在结节素空肾细胞缺乏膜定位的多囊蛋白-1和E-钙粘蛋白。这些数据表明，虽然Tsc 2肿瘤抑制基因功能的丧失破坏了正常的多囊蛋白-1功能和E-钙粘蛋白的膜定位，但正常的β-连环蛋白信号传导仍保留在结节蛋白缺失细胞中。(C)2002 Wiley-Liss，Inc.
The tuberous sclerosis (TSC) 2 tumor suppressor gene encodes the protein tuberin, which has recently been shown to play a crucial role in the intracellular trafficking of polycystin-1, the product of the polycystic kidney disease (PDK) 1 gene. PKD1 is responsible for most cases of autosomal dominant polycystic kidney disease, which has been described as "neoplasia in disguise." Polycystin-1 is a membrane protein localized to adherens junctions in a complex containing E-cadherin and alpha-, beta-,and gamma-catenins. To determine whether loss of membrane localization of polycystin-1 and E-cadherin affects the function of beta-catenin, beta-catenin localization and signaling were characterized in tuberin-null EKT2 and ERC15 cells and in tuberin-positive TRKE2 cells derived from polycystic, neoplastic, and normal rat kidney epithelial cells, respectively. EKT2 cells lacking tuberin because of inactivation of the Tsc2 gene fail to localize polycystin-1 and E-cadherin appropriately to these junctions. However, beta-catenin was retained at lateral cell membranes in both tuberin-null and tuberin-positive cells. Moreover, gene transcription mediated by beta-catenin T-cell-specific transcription factor complexes showed no differences among EKT2, ERC15, and TRKE2 cells. Thus, beta-catenin was stably retained at the lateral cell membrane in tuberin-null renal cells lacking membrane-localized polycystin-1 and E-cadherin. These data suggest that, although loss of Tsc2 tumor suppressor gene function disrupts normal polycystin-1 function and membrane localization of E-cadherin, normal beta-catenin signaling is retained in tuberin-null cells. (C) 2002 Wiley-Liss, Inc.