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J. Cell Biol. 150 (3): 567-580

Copyright © 2000 by the Rockefeller University Press.

Original Article

P120 Catenin Regulates the Actin Cytoskeleton via Rho Family Gtpases

Nicole K. Norena, Betty P. Liua, Keith Burridgea, , and Bertolt Krefta

a Department of Cell Biology and Anatomy and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599
Department of Cell Biology and Anatomy, 108 Taylor Hall, CB#7090, University of North Carolina, Chapel Hill, NC 27599-7090.(919) 966-1856(919) 966-5783


Abstract: Cadherins are calcium-dependent adhesion molecules responsible for the establishment of tight cell–cell contacts. p120 catenin (p120ctn) binds to the cytoplasmic domain of cadherins in the juxtamembrane region, which has been implicated in regulating cell motility. It has previously been shown that overexpression of p120ctn induces a dendritic morphology in fibroblasts (Reynolds, A.B., J. Daniel, Y. Mo, J. Wu, and Z. Zhang. 1996. Exp. Cell Res. 225:328–337.). We show here that this phenotype is suppressed by coexpression of cadherin constructs that contain the juxtamembrane region, but not by constructs lacking this domain. Overexpression of p120ctn disrupts stress fibers and focal adhesions and results in a decrease in RhoA activity. The p120ctn-induced phenotype is blocked by dominant negative Cdc42 and Rac1 and by constitutively active Rho-kinase, but is enhanced by dominant negative RhoA. p120ctn overexpression increased the activity of endogenous Cdc42 and Rac1. Exploring how p120ctn may regulate Rho family GTPases, we find that p120ctn binds the Rho family exchange factor Vav2. The behavior of p120ctn suggests that it is a vehicle for cross-talk between cell–cell junctions and the motile machinery of cells. We propose a model in which p120ctn can shuttle between a cadherin-bound state and a cytoplasmic pool in which it can interact with regulators of Rho family GTPases. Factors that perturb cell–cell junctions, such that the cytoplasmic pool of p120ctn is increased, are predicted to decrease RhoA activity but to elevate active Rac1 and Cdc42, thereby promoting cell migration.

Key Words: cadherin • Rac • guanine nucleotide exchange factor • Vav2 • migration

N. Noren and B. Kreft contributed equally to this paper.

B. Kreft's present address is Schering AG, Genomics/Bioinformatics, Muellerstr. 178, 13342 Berlin, Germany.

1Abbreviations used in this paper: DN, dominant negative; GAP, GTPase activating proteins; GEF, guanine nucleotide exchange factor; GFP, green fluorescent protein; p120ctn, p120 catenin.

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WASp deficiency in mice results in failure to form osteoclast sealing zones and defects in bone resorption.
Y. Calle, G. E. Jones, C. Jagger, K. Fuller, M. P. Blundell, J. Chow, T. Chambers, and A. J. Thrasher (2004)
Blood 103, 3552-3561
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Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth.
N. K. Noren, M. Lu, A. L. Freeman, M. Koolpe, and E. B. Pasquale (2004)
PNAS 101, 5583-5588
   Abstract »    Full Text »    PDF »
Vertebrate development requires ARVCF and p120 catenins and their interplay with RhoA and Rac.
X. Fang, H. Ji, S.-W. Kim, J.-I. Park, T. G. Vaught, P. Z. Anastasiadis, M. Ciesiolka, and P. D. McCrea (2004)
J. Cell Biol. 165, 87-98
   Abstract »    Full Text »    PDF »
Laminar Shear Stress Differentially Modulates Gene Expression of p120 Catenin, Kaiso Transcription Factor, and Vascular Endothelial Cadherin in Human Coronary Artery Endothelial Cells.
J. Kondapalli, A. S. Flozak, and M. L. C. Albuquerque (2004)
J. Biol. Chem. 279, 11417-11424
   Abstract »    Full Text »    PDF »
Cdc42 - the centre of polarity.
S. Etienne-Manneville (2004)
J. Cell Sci. 117, 1291-1300
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EGFR signaling to p120-catenin through phosphorylation at Y228.
D. J. Mariner, M. A. Davis, and A. B. Reynolds (2004)
J. Cell Sci. 117, 1339-1350
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A Novel Interaction between Kinesin and p120 Modulates p120 Localization and Function.
M. Yanagisawa, I. N. Kaverina, A. Wang, Y. Fujita, A. B. Reynolds, and P. Z. Anastasiadis (2004)
J. Biol. Chem. 279, 9512-9521
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C. M. Franz and A. J. Ridley (2004)
J. Biol. Chem. 279, 6588-6594
   Abstract »    Full Text »    PDF »
Epithelial Cell Polarity Alters Rho-GTPase Responses to Pseudomonas aeruginosa.
B. I. Kazmierczak, K. Mostov, and J. N. Engel (2004)
Mol. Biol. Cell 15, 411-419
   Abstract »    Full Text »    PDF »
Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.
J. Gavard, M. Lambert, I. Grosheva, V. Marthiens, T. Irinopoulou, J.-F. Riou, A. Bershadsky, and R.-M. Mege (2004)
J. Cell Sci. 117, 257-270
   Abstract »    Full Text »    PDF »
Two Regions of Cadherin Cytoplasmic Domains Are Involved in Suppressing Motility of a Mammary Carcinoma Cell Line.
M. Fedor-Chaiken, T. E. Meigs, D. D. Kaplan, and R. Brackenbury (2003)
J. Biol. Chem. 278, 52371-52378
   Abstract »    Full Text »    PDF »

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