5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis

5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis
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DOI:
10.1006/bbrc.2001.6288
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发表时间:
2002-01-25
影响因子:
3.1
通讯作者:
Stern, PL
Stern, PL
中科院分区:
生物学4区
文献类型:
--
作者:
Awan, A;Lucic, MR;Stern, PL

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5 T4跨膜糖蛋白的过表达可以对肌动蛋白细胞骨架和细胞迁移具有显著影响。使用酵母双杂交的方法,我们描述了一种新的5 T4和TIP-2/GIPC,胞质相互作用蛋白含有PDZ结构域之间的相互作用。5 T4的胞质尾区含有一个I类PDZ结合基序(Ser-Asp-瓦尔),我们证明了该区域,特别是末端缬氨酸,是5 T4与TIP-2/GIPC相互作用所必需的。表达血凝素标记的TIP-2/GIPC(HA-TIP-2/GIPC)的HeLa细胞具有改变的内源性5 T4分布,其与HA-TIP-2/GIPC共定位,从而支持相互作用。此外,TIP-2/GIPC可以与来自HeLa细胞裂解物的5 T4共免疫沉淀。5 T4和TIP-2/GIPC相互作用的鉴定提供了5 T4和肌动蛋白细胞骨架之间的第一个联系。由于其他蛋白质,如5 T4,与TIP-2/GIPC相关,并与癌症有关,我们探索TIP-2/GIPC可能是参与癌症过程的共同因素的可能性。(C)2002 Elsevier Science(美国)。
Overexpression of the 5T4 transmembrane glycoprotein can have marked effects on both the actin cytoskeleton and cell migration. Using a yeast two hybrid approach, we describe a novel interaction between 5T4 and TIP-2/GIPC, a cytoplasmic interacting protein containing a PDZ domain. The cytoplasmic tail of 5T4 contains a class I PDZ-binding motif (Ser-Asp-Val) and we demonstrate that this region, in particular the terminal valine, is required for 5T4 interaction with TIP-2/GIPC. HeLa cells expressing hemagglutinin-tagged TIP-2/GIPC (HA-TIP-2/GIPC) have an altered distribution of endogenous 5T4, which colocalizes with HA,-TIP-2/GIPC, thus supporting an interaction. Furthermore, TIP-2/GIPC can be coimmunoprecipitated with 5T4 from HeLa cell lysates. Identification of the 5T4 and TIP-2/GIPC interaction provides the first link between 5T4 and the actin cytoskeleton. Since other proteins, like 5T4, associate with TIP-2/GIPC and are linked with cancer, we explore the possibility that TIP-2/GIPC may be a common factor involved in the cancer process. (C) 2002 Elsevier Science (USA).