Polar Expression of ErbB-2/HER2 in Epithelia: Bimodal Regulation by Lin-7

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• 作者：Maya Shelly ; Yaron Mosesson ; Ami Citri ; Sara Lavi ; Yaara Zwang ; Naomi Melamed-Book ; Benjamin Aroeti ; Yosef Yarden
• 关键词：CELLBIO ; CELLCYCLE
• 刊名：Developmental Cell
• 出版年：2003
• 出版时间：September 2003
• 年：2003
• 卷：5
• 期：3
• 页码：475-486
• 全文大小：945 K

文摘

ErbB-2/HER2 drives epithelial malignancies by forming heterodimers with growth factor receptors. The primordial invertebrate receptor is sorted to the basolateral epithelial surface by binding of the PDZ domain of Lin-7 to the receptor's tail. We show that all four human ErbBs are basolaterally expressed, even when the tail motif is absent. Mutagenesis of hLin-7 unveiled a second domain, KID, that binds to the kinase region of ErbBs. The PDZ interaction mediates stabilization of ErbB-2 at the basolateral surface. On the other hand, binding of KID is involved in initial delivery to the basolateral surface, and in its absence, unprocessed ErbB-2 molecules are diverted to the apical surface. Hence, distinct domains of Lin-7 regulate receptor delivery to and maintenance at the basolateral surface of epithelia.