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Dev Cell. 2003 Sep;5(3):475-86.

Polar expression of ErbB-2/HER2 in epithelia. Bimodal regulation by Lin-7.

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1
Department of Biological Regulation, The Weizmann Institute of Science, 76100, Rehovot, Israel.

Abstract

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.

PMID:
12967566
[Indexed for MEDLINE]
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