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首页> 外文期刊>Molecular and Cellular Biology >Basolateral Targeting of ERBB2 Is Dependent on a Novel Bipartite Juxtamembrane Sorting Signal but Independent of the C-Terminal ERBIN-Binding Domain
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Basolateral Targeting of ERBB2 Is Dependent on a Novel Bipartite Juxtamembrane Sorting Signal but Independent of the C-Terminal ERBIN-Binding Domain

机译:ERBB2的基底外侧靶向依赖于新型的双近膜分选信号,但独立于C末端ERBIN结合域。

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ERBB2 is a receptor tyrosine kinase present on the basolateral membrane of polarized epithelia and has important functions in organ development and tumorigenesis. Using mutagenic analyses and Madin-Darby canine kidney (MDCK) cells, we have investigated the signals that regulate basolateral targeting of ERBB2. We show that basolateral delivery of ERBB2 is dependent on a novel bipartite juxtamembrane sorting signal residing between Gln-692 and Thr-701. The signal shows only limited sequence homology to known basolateral targeting signals and is both necessary and sufficient for correct sorting of ERBB2. In addition we demonstrate that this motif can function as a dominant basolateral targeting signal by its ability to redirect the apically localized P75 neurotrophin receptor to the basolateral membrane domain of polarized epithelial cells. Interestingly, LLC-PK1 cells, which are deficient for the μ1B subunit of the AP1B adaptor complex, missort a large proportion of ERBB2 to the apical membrane domain. This missorting can be partially corrected by the introduction of μ1B, suggesting a possible role for AP1B in ERBB2 endosomal trafficking. Furthermore, we find that the C-terminal ERBIN binding domain of ERBB2 is not necessary for its basolateral targeting in MDCK cells.
机译:ERBB2是存在于极化上​​皮的基底外侧膜上的受体酪氨酸激酶,在器官发育和肿瘤发生中具有重要作用。使用诱变分析和Madin-Darby犬肾(MDCK)细胞,我们研究了调节ERBB2基底外侧靶向的信号。我们显示ERBB2的基底外侧传递取决于驻留在Gln-692和Thr-701之间的新型双部分近膜分选信号。该信号仅显示与已知基底外侧靶向信号的有限序列同源性,并且对于正确分选ERBB2既必要又充分。另外,我们证明了该基序可以通过其将根尖定位的P75神经营养蛋白受体重定向至极化上皮细胞的基底外侧膜结构域的功能而充当基底外侧定向信号。有趣的是,缺少AP1B接头复合体的μ1B亚基的LLC-PK1细胞将很大比例的ERBB2错配到了顶端膜结构域。可以通过引入μ1B来部分纠正这种错漏,这表明AP1B在ERBB2内体运输中可能发挥作用。此外,我们发现,ERBB2的C端ERBIN结合域对于其在MDCK细胞中的基底外侧靶向不是必需的。

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