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EGFR phosphorylation-dependent formation of cell-cell contacts by Ras/Erks cascade inhibition

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Authors
Lee, Jung Weon; Kang, Eun-Sil; Oh, Min-A; Lee, Sin-Ae; Kim, Tae Young; Kim, Sung-Hoon; Gotoh, Noriko; Kim, Yong-Nyun
Issue Date
2007
Publisher
Elsevier
Citation
Biochim. Biophys. Acta 1773 (2007) 833-843
Keywords
Erk; EGFR; Cell–cell contacts; wound healing
Abstract
Cell–cell contacts play important roles in the homeostasis of normal epithelium and in the steps of metastasis of tumor cells, although signaling
mechanisms to regulate cell–cell contacts are unclear. In this study, we observed that phenotype of no cell–cell contacts in rat intestinal epithelial
cell subline (RIE1-Sca) correlated with increased Erk1/2 signaling activity, compared to that of parental RIE1 cells growing in colonies.
Furthermore, cell–cell contacts between RIE1-Sca cells were reformed by treatment with a specific MEK inhibitor (U0126), with translocation of
ZO1 and β-catenin to cell–cell contacts, without changes of their expression levels. U0126 treatment also increased EGFR phosphorylation in a
ligand-independent manner. Pretreatment with EGFR kinase inhibitor abolished U0126 treatment-mediated EGFR phosphorylation, and
expression of dominant negative H-Ras N17 allowed EGFR phosphorylation and cell–cell contacts even without U0126 treatment. Furthermore,
the expression of a nonphosphorylatable EGFR Y5F mutant abolished U0126-mediated cell–cell contacts. U0126 treatment also caused less
efficient wound healing by keeping monolayer integrity intact, compared to control untreated cells. This U0126-mediated reduction in wound
healing was further altered either by pretreatment of EGFR kinase inhibitor or expression of H-Ras N17 or EGFR Y5F. Taken together, this study
supports a unique mechanism of cell–cell contact formation through MEK/Erks inhibition-mediated EGFR phosphorylation.
ISSN
0167-4889
Language
English
URI
http://www.elsevier.com/locate/bbamcr
http://hdl.handle.net/10371/3241
DOI
https://doi.org/10.1016/j.bbamcr.2007.02.003
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
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