Association of Lbc Rho guanine nucleotide exchange factor with α-catenin-related protein, α-catulin/CTNNAL1, supports serum response factor activation
Association of Lbc Rho guanine nucleotide exchange factor with α-catenin-related protein, α-catulin/CTNNAL1, supports serum response factor activation
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DOI：
10.1074/jbc.m202447200
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发表时间：
2002-11-22
影响因子：
4.8
通讯作者：
Toksoz, D
中科院分区：
文献类型：
--
作者：
Park, B;Nguyen, NT;Toksoz, D
Rho GTPase信号通路是肌动蛋白细胞骨架组织和血清反应因子依赖性基因转录所需的。Lbc是一种Rho特异性鸟嘌呤核苷酸交换因子，含有一个调节性C-末端区域。为了阐明Lbc调节机制，进行了与Lbc C-末端区域相互作用的蛋白质的酵母双杂交筛选，导致编码相同的734-氨基酸Lbc相互作用蛋白的cDNA的多重分离。Lbc相互作用蛋白与α-连环蛋白细胞粘附组分具有同源性，并且与功能未知的α-连环蛋白样α-catulin蛋白相同。人类α-catulin基因（CTNNAL 1）定位于9 q31 -32。在这里，我们确定了预测的内源性α-catulin产品，文件α-catulin和Lbc在多种人类细胞系的共表达，并显示α-catulin和Lbc亚细胞共分级和细胞内定位。绘制了Lbc和α-catulin相互作用所需的区域，并检测了哺乳动物细胞中Lbc和α-catulin之间的复合物形成。在功能上，α-catulin共表达导致体内Lbc诱导的血清应答因子活化增加，如通过转录报告基因测定所测量的。此外，α-catulin共表达增强Lbc诱导的体内GTP-Rho形成。这些结果支持的概念，最近确定的α-catulin蛋白可以调节Rho通路信号在体内通过提供一个支架的Lbc Rho鸟嘌呤核苷酸交换因子。
The Rho GTPase signaling pathway is required for actin cytoskeletal organization and serum response factor-dependent gene transcription. Lbc is a Rho-specific guanine nucleotide exchange factor that contains a modulatory C-terminal region. To elucidate Lbc regulatory mechanism(s), a yeast two-hybrid screen for proteins that interact with the Lbc C-terminal region was carried out, resulting in multiple isolation of cDNAs encoding the same 734-amino acid Lbc interacting protein. The Lbc interacting protein has homology with the alpha-catenin cell adhesion component and is identical to the alpha-catenin-like alpha-catulin protein of unknown function. The human alpha-catulin gene (CTNNAL1) maps to 9q31-32. Here we identify the predicted endogenous alpha-catulin product, document alpha-catulin and Lbc co-expression in multiple human cell lines, and show alpha-catulin and Lbc subcellular co-fractionation and intracellular localization. The required regions for Lbc and alpha-catulin interaction were mapped, and complex formation between Lbc and alpha-catulin in mammalian cells was detected. Functionally, alpha-catulin co-expression leads to increased Lbc-induced serum response factor activation in vivo as measured by a transcriptional reporter assay. Furthermore, alpha-catulin co-expression enhances Lbc-induced GTP-Rho formation in vivo. These results support the concept that the recently identified alpha-catulin protein may modulate Rho pathway signaling in vivo by providing a scaffold for the Lbc Rho guanine nucleotide exchange factor.