Open AccessEpidermal growth factor receptor and integrins control force-dependent vinculin recruitment to E-Cadherin junctions
Author(s) -
Poonam Sehgal,
Xinyu Kong,
Jun Wu,
Raimon Sunyer,
Xavier Trepat,
Deborah Leckband
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.206656
Subject(s) - vinculin , biology , microbiology and biotechnology , cadherin , integrin , signal transduction , tyrosine kinase , phosphorylation , tyrosine phosphorylation , epidermal growth factor receptor , cancer research , receptor , focal adhesion , biochemistry , cell
This study reports novel findings that link E-Cadherin-mediated force-transduction signaling to vinculin targeting to intercellular junctions via epidermal growth factor receptor (EGFR) and integrins. These results build on previous findings, which demonstrated that mechanically perturbed E-Cadherin receptors activate phosphoinositide-3-kinase and downstream integrins, in an EGFR-dependent manner. Results of this study show that this EGFR-mediated kinase cascade controls the force-dependent recruitment of vinculin to stressed E-Cadherin complexes--a key early signature of cadherin-based mechanotransduction. Vinculin targeting requires phosphorylation at tyrosine 822 by Abelson family kinase (Abl), but the origin of force-dependent Abl activation had not been identified. We now present evidence that integrin activation, which is downstream from EGFR signaling controls Abl activation, thus linking E-Cadherin to Abl through a mechanosensitive signaling network. These findings place EGFR and integrins at the center of a positive feedback loop, through which force-activated E-Cadherin signals regulate vinculin recruitment to cadherin complexes, in response to increased intercellular tension.