Format

Send to

Choose Destination
J Cell Sci. 2018 Dec 14;131(24). pii: jcs216648. doi: 10.1242/jcs.216648.

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

Author information

1
Department of Biochemistry and the Interdisciplinary Program in Molecular and Cellular Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
2
Department of Biochemistry and the Interdisciplinary Program in Molecular and Cellular Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA kris-demali@uiowa.edu.

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.

KEYWORDS:

Cell stiffening; E-cadherin; Force; SHP-2; Vinculin

PMID:
30478196
PMCID:
PMC6307880
[Available on 2019-12-15]
DOI:
10.1242/jcs.216648
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center