Date of Degree
Access restricted until 07/03/2020
PhD (Doctor of Philosophy)
Molecular and Cell Biology
Kris A. DeMali
First Committee Member
John G. Koland
Second Committee Member
Dawn E. Quelle
Third Committee Member
Mark A. Stamnes
Fourth Committee Member
Tina L. Tootle
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
Heidema, Christy Rose. "Shp2 is activated in response to force on E-cadherin and dephosphorylates vinculin Y822." PhD (Doctor of Philosophy) thesis, University of Iowa, 2018.
Available for download on Friday, July 03, 2020