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Inhibition of RhoA by p120 catenin

Nature Cell Biology volume 2, pages 637–644 (2000)Cite this article

Abstract

RhoA organizes actin stress fibres and is necessary for cell transformation by oncogenes such as src and ras. Moreover, RhoA is implicated in cadherin clustering during the formation of adherens junctions. The catenin p120 has also been implicated in cadherin clustering through an unknown mechanism. Here we show that p120 selectively inhibits RhoA activity in vitro and in vivo. RhoA inhibition and the interaction of p120 with cadherins are mutually exclusive, suggesting a mechanism for regulating the recruitment and exchange of RhoA at nascent cell–cell contacts. By affecting RhoA activation, p120 could modulate cadherin functions, including suppression of invasion, neurite extension and junction formation.

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Figure 1: Inhibition of p120-induced branching by DA RhoA.
Figure 2: RhoA inhibition and p120 overexpression have similar consequences in cells.
Figure 3: p120-overexpressing cells do not respond to LPA stimulation, consistent with the ability of recombinant p120 to affect RhoA activation in vitro .
Figure 4: Inhibition of intrinsic or GEF-induced activation of RhoA by wild-type p120 but not by the p120Δ(662–628) mutant.
Figure 5: Functional relationships between E-cadherin, p120, RhoA and ezrin.

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Acknowledgements

A.B.R. was supported in part by NIH grant CA55724 and by the Ingram-Vanderbilt Cancer Center through the Cancer Center support grant CA69485. Y.Z. was supported by NIH grant GM53943. We thank M.A. Schwartz for the GST–RBD construct, M. Symons for Rho family GTPase constructs and helpful discussions and J.M. Daniel for the p120–GST construct and general support.

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Authors and Affiliations

  1. Department of Cell Biology, Vanderbilt University, MCN C-2310, Nashville, 37232-2175 , Tennessee, USA

    Panos Z. Anastasiadis, Molly A. Thoreson, Debbie J. Mariner, Howard C. Crawford & Albert B. Reynolds

  2. Department of Biochemistry, University of Tennessee, Memphis, 38163, Tennessee, USA

    Sun Y. Moon & Yi Zheng

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Correspondence to Albert B. Reynolds.

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Anastasiadis, P., Moon, S., Thoreson, M. et al. Inhibition of RhoA by p120 catenin. Nat Cell Biol 2, 637–644 (2000). https://doi.org/10.1038/35023588

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