Epidermal growth factor receptor and integrins control forcedependent vinculin recruitment to E-cadherin junctions

Poonam Sehgal, Xinyu Kong, Jun Wu, Raimon Sunyer, Xavier Trepat, Deborah E Leckband

Research output: Contribution to journalArticle

Abstract

This study reports novel findings that link E-cadherin (also known as CDH1)-mediated force-transduction signaling to vinculin targeting to intercellular junctions via epidermal growth factor receptor (EGFR) and integrins. These results build on previous findings that 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 its phosphorylation at tyrosine 822 by Abl family kinases (hereafter Abl), but the origin of forcedependent Abl activation had not been identified. We now present evidence that integrin activation, which is downstream of 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.

Original languageEnglish (US)
Article numberjcs206656
JournalJournal of cell science
Volume131
Issue number6
DOIs
StatePublished - Mar 1 2018

Fingerprint

Vinculin
Cadherins
Epidermal Growth Factor Receptor
Integrins
1-Phosphatidylinositol 4-Kinase
Intercellular Junctions
Tyrosine
Phosphotransferases
Phosphorylation

Keywords

  • Cadherin
  • Epidermal growth factor receptor
  • Force transduction
  • Integrin
  • Magnetic twisting cytometry
  • Vinculin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Epidermal growth factor receptor and integrins control forcedependent vinculin recruitment to E-cadherin junctions. / Sehgal, Poonam; Kong, Xinyu; Wu, Jun; Sunyer, Raimon; Trepat, Xavier; Leckband, Deborah E.

In: Journal of cell science, Vol. 131, No. 6, jcs206656, 01.03.2018.

Research output: Contribution to journalArticle

Sehgal, Poonam ; Kong, Xinyu ; Wu, Jun ; Sunyer, Raimon ; Trepat, Xavier ; Leckband, Deborah E. / Epidermal growth factor receptor and integrins control forcedependent vinculin recruitment to E-cadherin junctions. In: Journal of cell science. 2018 ; Vol. 131, No. 6.
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