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.
| Identifer | oai:union.ndltd.org:uiowa.edu/oai:ir.uiowa.edu:etd-7824 |
| Date | 01 May 2018 |
| Creators | Heidema, Christy Rose |
| Contributors | DeMali, Kris A. |
| Publisher | University of Iowa |
| Source Sets | University of Iowa |
| Language | English |
| Detected Language | English |
| Type | dissertation |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | Copyright © 2018 Christy Rose Heidema |
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