| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 279, Issue 43, 44490-44496, October 22, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the
Unité Mixte Recherche 146, Centre National de la Recherche Scientifique, B
timent 110, Centre Universitaire, 91405 Orsay, France
Induction of epithelial cell motility is a fundamental morphogenetic event that is recapitulated during carcinoma metastasis. Random motility of NBT-II carcinoma cells on collagen critically depends on paxillin phosphorylation at Tyr-31 and Tyr-118, the binding sites for the adapter protein CrkII. Two constitutive partners of CrkII are the exchange factors DOCK180 and C3G. CrkII bound to DOCK180 formed a signaling complex with phosphorylated paxillin that was necessary for cell migration as inferred from the inhibition caused by a DOCK180-interfering mutant. DOCK180, which acts predominantly on the Rho family GTPase Rac1, restored cell locomotion in cells expressing Phe-31/118 paxillin mutants deficient in Rac1 GTP-loading, suggesting that formation of paxillin-Crk-DOCK180 signaling complex controls collagen-dependent migration mainly through Rac1 activation. In migrating cells, CrkII constitutive association with C3G was not sufficient to stimulate its GDP/GTP exchange activity toward the Ras family GTPase Rap1. However, when constitutively active RapV12 was overexpressed, it negatively regulated cell motility. Activation of the C3G/Rap1 signaling pathway resulted in down-regulation of the paxillin-Crk-DOCK180 complex and reduction of Rac1-GTP, suggesting that Rap1 activation could suppress the Rac1 signaling pathway in epithelial cells.
Received for publication, May 10, 2004 , and in revised form, July 22, 2004.
* This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Association pour la Recherche sur le cancer (ARC 5782), and Astra Zeneca Pharma, S.A. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.
To whom correspondence should be addressed. Tel.: 33-1-69-86-71-77; Fax: 33-1-69-86-30-51; E-mail: ana-maria.valles{at}curie.u-psud.fr.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  N. O. Deakin and C. E. Turner Paxillin comes of age J. Cell Sci., August 1, 2008; 121(15): 2435 - 2444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Takahashi, Y. Rikitake, Y. Nagamatsu, T. Hara, W. Ikeda, K.-i. Hirata, and Y. Takai Sequential activation of Rap1 and Rac1 small G proteins by PDGF locally at leading edges of NIH3T3 cells. Genes Cells, June 1, 2008; 13(6): 549 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Monami, E. M. Gonzalez, M. Hellman, L. G. Gomella, R. Baffa, R. V. Iozzo, and A. Morrione Proepithelin Promotes Migration and Invasion of 5637 Bladder Cancer Cells through the Activation of ERK1/2 and the Formation of a Paxillin/FAK/ERK Complex. Cancer Res., July 15, 2006; 66(14): 7103 - 7110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shintani, M. J. Wheelock, and K. R. Johnson Phosphoinositide-3 Kinase-Rac1-c-Jun NH2-terminal Kinase Signaling Mediates Collagen I-induced Cell Scattering and Up-Regulation of N-Cadherin Expression in Mouse Mammary Epithelial Cells Mol. Biol. Cell, July 1, 2006; 17(7): 2963 - 2975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Jamieson, D. A. Tumbarello, M. Halle, M. C. Brown, M. L. Tremblay, and C. E. Turner Paxillin is essential for PTP-PEST-dependent regulation of cell spreading and motility: a role for paxillin kinase linker J. Cell Sci., December 15, 2005; 118(24): 5835 - 5847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Sloan, J. K. Stewart, A. F. Treloar, R. T. Matthews, and D. G. Jay CD155/PVR Enhances Glioma Cell Dispersal by Regulating Adhesion Signaling and Focal Adhesion Dynamics Cancer Res., December 1, 2005; 65(23): 10930 - 10937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Meller, S. Merlot, and C. Guda CZH proteins: a new family of Rho-GEFs J. Cell Sci., November 1, 2005; 118(21): 4937 - 4946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Balzac, M. Avolio, S. Degani, I. Kaverina, M. Torti, L. Silengo, J. V. Small, and S. F. Retta E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between cadherin and integrin function J. Cell Sci., October 15, 2005; 118(20): 4765 - 4783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zaidel-Bar, Z. Kam, and B. Geiger Polarized downregulation of the paxillin-p130CAS-Rac1 pathway induced by shear flow J. Cell Sci., September 1, 2005; 118(17): 3997 - 4007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Brown, L. A. Cary, J. S. Jamieson, J. A. Cooper, and C. E. Turner Src and FAK Kinases Cooperate to Phosphorylate Paxillin Kinase Linker, Stimulate Its Focal Adhesion Localization, and Regulate Cell Spreading and Protrusiveness Mol. Biol. Cell, September 1, 2005; 16(9): 4316 - 4328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Tang, W. Zhang, and S. J. Gunst The Adapter Protein CrkII Regulates Neuronal Wiskott-Aldrich Syndrome Protein, Actin Polymerization, and Tension Development during Contractile Stimulation of Smooth Muscle J. Biol. Chem., June 17, 2005; 280(24): 23380 - 23389. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
