SHP-2 is activated in response to force on E-cadherin and dephosphorylates vinculin Y822

Hannah Campbell; Christy Heidema; Daisy G Pilarczyk; Kris A DeMali

doi:10.1242/jcs.216648

Back

SHP-2 is activated in response to force on E-cadherin and dephosphorylates vinculin Y822

Journal article

Open access

Peer reviewed

SHP-2 is activated in response to force on E-cadherin and dephosphorylates vinculin Y822

Hannah Campbell, Christy Heidema, Daisy G Pilarczyk and Kris A DeMali

Journal of cell science, Vol.131(24), jcs216648

12/14/2018

DOI: 10.1242/jcs.216648

PMCID: PMC6307880

PMID: 30478196

Files and links (1)

url

https://doi.org/10.1242/jcs.216648View

Published (Version of record) Open Access

Abstract

The response of cells to mechanical inputs is a key determinant of cell behavior. In response to external forces, E-cadherin initiates signal transduction cascades that allow the cell to modulate its contractility to withstand the force. Much attention has focused on identifying the E-cadherin signaling pathways that promote contractility, but the negative regulators remain undefined. In this study, we identify SHP-2 as a force-activated phosphatase that negatively regulates E-cadherin force transmission by dephosphorylating vinculin Y822. To specifically probe a role for SHP-2 in E-cadherin mechanotransduction, we mutated vinculin so that it retains its phosphorylation but cannot be dephosphorylated. Cells expressing the mutant vinculin have increased contractility. This work provides a mechanism for inactivating E-cadherin mechanotransduction and provides a new method for specifically targeting the action of phosphatases in cells.

Phosphorylation

Actins - metabolism

alpha Catenin - metabolism

Cadherins - metabolism

Cell Adhesion - physiology

Cytoskeleton - metabolism

Humans

Mechanotransduction, Cellular - physiology

Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism

Vinculin - metabolism

Details

Title: Subtitle: SHP-2 is activated in response to force on E-cadherin and dephosphorylates vinculin Y822
Creators: Hannah Campbell - Roy J. and Lucille A. Carver College of Medicine
Christy Heidema - Roy J. and Lucille A. Carver College of Medicine
Daisy G Pilarczyk - Roy J. and Lucille A. Carver College of Medicine
Kris A DeMali - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.131(24), jcs216648
DOI: 10.1242/jcs.216648
PMID: 30478196
PMCID: PMC6307880
ISSN: 0021-9533
eISSN: 1477-9137
Grant note: R01 GM112805 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 12/14/2018
Academic Unit: Dermatology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984293082002771

Metrics

11 Record Views

3 Times Cited - Web of Science

See more details