Document Type


Date of Degree

Spring 2018

Access Restrictions

Access restricted until 07/03/2020

Degree Name

PhD (Doctor of Philosophy)

Degree In

Molecular and Cell Biology

First Advisor

DeMali, Kris A

First Committee Member

Koland, John G

Second Committee Member

Quelle, Dawn E

Third Committee Member

Stamnes, Mark A

Fourth Committee Member

Tootle, Tina L


The response of cells to mechanical inputs is a key determinant of cell behavior. In response to changes in the mechanical environment of epithelial cells, E-cadherin initiates signal transduction cascades that allow the cells to modulate their 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 thesis, we identify SHP2 as a force-activated phosphatase that negatively regulates E-cadherin force transmission by dephosphorylating vinculin Y822. To specifically probe a role for SHP2 in E-cadherin mechanotransduction, we innovatively mutated vinculin so that it retains its phosphorylation but cannot be dephosphorylated. Cells expressing the mutant vinculins have increased contractility. This work provides the first mechanism for inactivating E-cadherin mechanotransduction and provides a new method for specifically targeting the action of phosphatases in cells.


E-cadherin, Force, SHP2, Stiffening, Vinculin


xvii, 161 pages


Includes bibliographical references.


Copyright © 2018 Christy Rose Heidema