![[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}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 14, Issue 7, 2818-2831, July 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-PIX Complex and Promotes Rac-dependent Relocalization of Paxillin to Focal Contacts
||
Molecular Oncology Group, McGill University Health Centre, Departments of
*Biochemistry,
Medicine, and Oncology, McGill University,
Montreal, Quebec, Canada H3A 1A1; and
Department of Cell and Developmental Biology,
SUNY Upstate Medical University, Syracuse, New York 13210
Submitted August 16, 2002;
Revised February 12, 2003;
Accepted February 13, 2003
Monitoring Editor: Suzanne Pfeffer
We have previously demonstrated that the CrkII and CrkL adapter proteins
are required for the spreading of epithelial colonies and the breakdown of
adherens junctions in response to hepatocyte growth factor. When
overexpressed, CrkII and CrkL promote lamellipodia formation, cell spreading,
and the loss of epithelial adherens junctions in the absence of hepatocyte
growth factor. The exact mechanism by which Crk proteins elicit these changes
is unclear. We show that the overexpression of CrkII or CrkL, but not Src
homology 2 or amino-terminal Src homology 3 domain mutant Crk proteins,
promotes the relocalization of Paxillin to focal contacts throughout the cell
and within lamellipodia in a Rac-dependent manner. In stable cell lines
overexpressing CrkII, enhanced lamellipodia formation and cell spreading
correlate with an increased association of CrkII with Paxillin, GIT2 (an
ARF-GAP) and 
-PIX (a Rac1 exchange factor). Mutants of Paxillin that
fail to associate with Crk or GIT2, or do not target to focal adhesions
inhibit Crk-dependent cell spreading and lamellipodia formation. We conclude
from these studies that the association of Crk with Paxillin is important for
the spreading of epithelial colonies, by influencing the recruitment of
Paxillin to focal complexes and promoting the enhanced assembly of
Paxillin/GIT2/-PIX complexes.
Abbreviations used: ARF, ADP-ribosylation factor; EM, epithelial-mesenchymal; FBS, fetal bovine serum; GAP, GTPase activating protein; GTPase, guanosine triphosphatase; HGF, hepatocyte growth factor; MDCK, Madin-Darby canine kidney; PBS, phosphate-buffered saline; SH2, Src homology 2; SH3, Src homology 3.
|| Corresponding author. E-mail address: morag.park{at}mcgill.ca.
This article has been cited by other articles:
|
|
 |
|
  M. T. Herrera Abreu, P. Castellanos Penton, V. Kwok, E. Vachon, D. Shalloway, L. Vidali, W. Lee, C. A. McCulloch, and G. P. Downey Tyrosine phosphatase PTP{alpha} regulates focal adhesion remodeling through Rac1 activation Am J Physiol Cell Physiol, April 1, 2008; 294(4): C931 - C944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Chianale, S. Cutrupi, E. Rainero, G. Baldanzi, P. E. Porporato, S. Traini, N. Filigheddu, V. F. Gnocchi, M. M. Santoro, O. Parolini, et al. Diacylglycerol Kinase-{alpha} Mediates Hepatocyte Growth Factor-induced Epithelial Cell Scatter by Regulating Rac Activation and Membrane Ruffling Mol. Biol. Cell, December 1, 2007; 18(12): 4859 - 4871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Totaro, S. Paris, C. Asperti, and I. de Curtis Identification of an Intramolecular Interaction Important for the Regulation of GIT1 Functions Mol. Biol. Cell, December 1, 2007; 18(12): 5124 - 5138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Avraamides, M. E. Bromberg, J. P. Gaughan, S. M. Thomas, A. Y. Tsygankov, and T. S. Panetti Hic-5 promotes endothelial cell migration to lysophosphatidic acid Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H193 - H203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Achiwa and J. S. Lazo PRL-1 Tyrosine Phosphatase Regulates c-Src Levels, Adherence, and Invasion in Human Lung Cancer Cells Cancer Res., January 15, 2007; 67(2): 643 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Boulter, D. Grall, S. Cagnol, and E. Van Obberghen-Schilling Regulation of cell-matrix adhesion dynamics and Rac-1 by integrin linked kinase FASEB J, July 1, 2006; 20(9): 1489 - 1491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Burridge, S. K. Sastry, and J. L. Sallee Regulation of Cell Adhesion by Protein-tyrosine Phosphatases: I. CELL-MATRIX ADHESION J. Biol. Chem., June 9, 2006; 281(23): 15593 - 15596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Hoefen and B. C. Berk The multifunctional GIT family of proteins. J. Cell Sci., April 15, 2006; 119(Pt 8): 1469 - 1475. [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]
|
|
|
|
|
|
Q. Deng, J. Sun, and J. T. Barbieri Uncoupling Crk Signal Transduction by Pseudomonas Exoenzyme T J. Biol. Chem., October 28, 2005; 280(43): 35953 - 35960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Tumbarello, M. C. Brown, S. E. Hetey, and C. E. Turner Regulation of paxillin family members during epithelial-mesenchymal transformation: a putative role for paxillin {delta} J. Cell Sci., October 15, 2005; 118(20): 4849 - 4863. [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]
|
|
|
|
|
|
M. A. Sanders and M. D. Basson p130cas but Not Paxillin Is Essential for Caco-2 Intestinal Epithelial Cell Spreading and Migration on Collagen IV J. Biol. Chem., June 24, 2005; 280(25): 23516 - 23522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Rodrigues, K. E. Fathers, G. Chan, D. Zuo, F. Halwani, S. Meterissian, and M. Park CrkI and CrkII Function as Key Signaling Integrators for Migration and Invasion of Cancer Cells Mol. Cancer Res., April 1, 2005; 3(4): 183 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Y. Chen, C.-H. Shen, Y.-T. Tsai, F.-C. Lin, Y.-P. Huang, and R.-H. Chen Brk Activates Rac1 and Promotes Cell Migration and Invasion by Phosphorylating Paxillin Mol. Cell. Biol., December 15, 2004; 24(24): 10558 - 10572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Hinsby, J. V. Olsen, and M. Mann Tyrosine Phosphoproteomics of Fibroblast Growth Factor Signaling: A ROLE FOR INSULIN RECEPTOR SUBSTRATE-4 J. Biol. Chem., November 5, 2004; 279(45): 46438 - 46447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Brown and C. E. Turner Paxillin: Adapting to Change Physiol Rev, October 1, 2004; 84(4): 1315 - 1339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Schroter, S. Lier, A. Holz, S. Bogdan, C. Klambt, L. Beck, and R. Renkawitz-Pohl kette and blown fuse interact genetically during the second fusion step of myogenesis in Drosophila Development, September 15, 2004; 131(18): 4501 - 4509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bougneres, S. E. Girardin, S. A. Weed, A. V. Karginov, J.-C. Olivo-Marin, J. T. Parsons, P. J. Sansonetti, and G. T. Van Nhieu Cortactin and Crk cooperate to trigger actin polymerization during Shigella invasion of epithelial cells J. Cell Biol., July 19, 2004; 166(2): 225 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Stofega, L. C. Sanders, E. M. Gardiner, and G. M. Bokoch Constitutive p21-activated Kinase (PAK) Activation in Breast Cancer Cells as a Result of Mislocalization of PAK to Focal Adhesions Mol. Biol. Cell, June 1, 2004; 15(6): 2965 - 2977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Haglund, I. Ivankovic-Dikic, N. Shimokawa, G. D. Kruh, and I. Dikic Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites J. Cell Sci., May 15, 2004; 117(12): 2557 - 2568. [Abstract] [Full Text] [PDF]
|
|
