Open AccessSHP-2 is activated in response to force on E-cadherin and dephosphorylates vinculin Y822
Author(s) -
Hannah Campbell,
Christy Heidema,
Daisy G. Pilarczyk,
Kris A. DeMali
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.216648
Subject(s) - mechanotransduction , vinculin , cadherin , contractility , biology , microbiology and biotechnology , phosphorylation , signal transduction , phosphatase , cell , focal adhesion , biochemistry , endocrinology
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.