![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on April 1, 2007
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 27, 2006
Revised on December 26, 2006
Accepted on January 5, 2007
Department of Biochemistry and Molecular Biology, Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-7696
Monitoring Editor: Martin A. Schwartz
Using phage display we identified NHERF-2 as a novel binding partner for the cadherin associated protein, b-catenin. We showed that the second of two PDZ domains of NHERF interacts with a PDZ binding motif at the very carboxyl-terminus of b-catenin. N-cadherin expression has been shown to induce motility in a number of cell types. The first PDZ domain of NHERF is known to bind PDGF-Rb, and the interaction of PDGF-Rb with NHERF leads to enhanced cell spreading and motility. Here we show that b-catenin and N-cadherin are in a complex with NHERF and PDGF-Rb at membrane ruffles in the highly invasive fibrosarcoma cell line, HT1080. Using a stable shRNA system we showed that HT1080 cells knocked down for either N-cadherin or NHERF had impaired ability to migrate into the wounded area in a scratch assay, similar to cells treated with a PDGF-R kinase inhibitor. Cells expressing a mutant NHERF that is unable to associate with b-catenin had increased stress fibers, reduced lamellipodia and impaired cell migration. Using HeLa cells, which express little to no PDGF-R, we introduced PDGF-Rb and showed that it coimmunoprecipitates with N-cadherin, and that PDGF-dependent cell migration was reduced in these cells when we knocked-down expression of N-cadherin or NHERF. These studies implicate N-cadherin and b-catenin in cell migration via PDGF-R mediated signaling through the scaffolding molecule NHERF.
This article has been cited by other articles:
|
|
 |
|
  M. D. David, A. Yeramian, M. Dunach, M. Llovera, C. Canti, A. G. de Herreros, J. X. Comella, and J. Herreros Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential {beta}-catenin phosphorylation J. Cell Sci., August 15, 2008; 121(16): 2718 - 2730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Andrae, R. Gallini, and C. Betsholtz Role of platelet-derived growth factors in physiology and medicine Genes & Dev., May 15, 2008; 22(10): 1276 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Wang, Y. Yang, and P. A. Friedman Na/H Exchange Regulatory Factor 1, a Novel AKT-associating Protein, Regulates Extracellular Signal-regulated Kinase Signaling through a B-Raf-Mediated Pathway Mol. Biol. Cell, April 1, 2008; 19(4): 1637 - 1645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Wheelock, Y. Shintani, M. Maeda, Y. Fukumoto, and K. R. Johnson Cadherin switching J. Cell Sci., March 15, 2008; 121(6): 727 - 735. [Abstract] [Full Text] [PDF]
|
|
