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Title page for ETD etd-03062007-090915


Type of Document Dissertation
Author Wildenberg, Gregg Anthony
Author's Email Address gregg.wildenberg@vanderbilt.edu
URN etd-03062007-090915
Title p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho
Degree PhD
Department Cancer Biology
Advisory Committee
Advisor Name Title
Professor Albert Reynolds Committee Chair
Asst. Professor Alissa Weaver Committee Member
Asst. Professor Anne Kenworthy Committee Member
Professor Lynn Matrisian Committee Member
Professor Vito Quaranta Committee Member
Keywords
  • p190RhoGAP
  • p120-catenin
  • cell-cell adhesion
  • cell motility
  • cancer
  • RhoGTPase
  • cadherin
  • Cell adhesion -- Molecular aspects
Date of Defense 2006-11-20
Availability unrestricted
Abstract
Integration of receptor tyrosine kinase, integrin, and cadherin activities is crucial for normal cell growth, motility and adhesion. Here, we describe novel roles for p120 catenin (p120) and p190RhoGAP that coordinate crosstalk between these systems and regulate cadherin function. Surprisingly, PDGFR induced actin remodeling in NIH3T3 cells is blocked in the absence of p120, and the cells are partially transformed via constitutive activation of Rho. We have traced the mechanism to unexpected codependent roles for p120 and p190RhoGAP in regulating Rac-dependent antagonism of Rho. Receptor-induced Rac activity causes translocation of p190RhoGAP to adherens junctions (AJs), where it couples to the cadherin complex via interaction with p120. AJ formation is dependent on this p120-p190RhoGAP interaction and fails altogether if either of these proteins are compromised. We propose that Rac activation links diverse signaling systems to AJ assembly by controlling transient p190RhoGAP interactions with p120 and localized inhibition of Rho.
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