Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E05-12-1158 on June 7, 2006

Vol. 17, Issue 8, 3508-3520, August 2006

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
E05-12-1158v1
17/8/3508    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Le Boeuf, F.
Right arrow Articles by Huot, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Le Boeuf, F.
Right arrow Articles by Huot, J.

Phosphorylation of Focal Adhesion Kinase (FAK) on Ser732 Is Induced by Rho-dependent Kinase and Is Essential for Proline-rich Tyrosine Kinase-2–mediated Phosphorylation of FAK on Tyr407 in Response to Vascular Endothelial Growth FactorFormula

Fabrice Le Boeuf*, François Houle*, Mark Sussman{dagger}, and Jacques Huot*

*Le Centre de Recherche en Cancérologie de l’Université Laval, Québec, Québec G1R-2J6, Canada; and {dagger}Department of Biology, San Diego State University Heart Institute, San Diego State University, San Diego, CA 92182

Submitted December 20, 2005; Revised May 4, 2006; Accepted May 25, 2006
Monitoring Editor: Mark Ginsberg

Focal adhesion kinase (FAK) is phosphorylated on tyrosine and serine residues after cell activation. In the present work, we investigated the relationship between tyrosine and serine phosphorylation of FAK in promoting endothelial cell migration in response to vascular endothelial growth factor (VEGF). We found that VEGF induces the activation of the Rho-dependent kinase (ROCK) downstream from vascular endothelial growth factor receptor (VEGFR) 2. In turn, activated ROCK directly phosphorylates FAK on Ser732. Proline-rich tyrosine kinase-2 (Pyk2) is also activated in response to VEGF. Its activation requires the clustering of integrin {alpha}vbeta3 and triggers directly the phosphorylation of Tyr407 within FAK, an event necessary for cell migration. Interestingly, ROCK-mediated phosphorylation of Ser732 is essential for Pyk2-dependent phosphorylation of Tyr407, because the latter is abrogated in cells expressing a FAK mutant that is nonphosphorylatable on Ser732. We suggest that VEGF elicits the activation of the VEGFR2–ROCK pathway, leading to phosphorylation of Ser732 within FAK. In turn, phosphorylation of Ser732 would change the conformation of FAK, making it accessible to Pyk2 activated in response to its association with integrin beta3. Then, activated Pyk2 triggers the phosphorylation of FAK on Tyr407, promoting cell migration.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-12-1158) on June 7, 2006.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Jacques Huot ( jacques.huot{at}phc.ulaval.ca)

Abbreviations used: BAEC, bovine aortic endothelial cell; GAPDH, glyceraldehyde-3-phosphate-dehydrogenase; FAT, focal adhesion targeting; FERM, protein four.1, ezrin, radixin, moesin; FRNK, FAK related nonkinase domain; HSP90, heat-shock protein of 90 kDa; HUVEC, human umbilical vein endothelial cell; MLC, myosin light chain; Pyk2, proline-rich tyrosine kinase-2; ROCK, Rho-dependent kinase; VEGF, vascular endothelial growth factor.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. Y. J. Park, T.-L. Shen, S. Chien, and J.-L. Guan
Role of Focal Adhesion Kinase Ser-732 Phosphorylation in Centrosome Function during Mitosis
J. Biol. Chem., April 3, 2009; 284(14): 9418 - 9425.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. A. Birukova, N. Moldobaeva, J. Xing, and K. G. Birukov
Magnitude-dependent effects of cyclic stretch on HGF- and VEGF-induced pulmonary endothelial remodeling and barrier regulation
Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L612 - L623.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
E. Ispanovic, D. Serio, and T. L. Haas
Cdc42 and RhoA have opposing roles in regulating membrane type 1-matrix metalloproteinase localization and matrix metalloproteinase-2 activation
Am J Physiol Cell Physiol, September 1, 2008; 295(3): C600 - C610.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
G. Serini, L. Napione, M. Arese, and F. Bussolino
Besides adhesion: new perspectives of integrin functions in angiogenesis
Cardiovasc Res, May 1, 2008; 78(2): 213 - 222.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Cetin, C. L. Leaphart, J. Li, I. Ischenko, M. Hayman, J. Upperman, R. Zamora, S. Watkins, H. R. Ford, J. Wang, et al.
Nitric oxide inhibits enterocyte migration through activation of RhoA-GTPase in a SHP-2-dependent manner
Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1347 - G1358.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
L. Lamalice, F. Le Boeuf, and J. Huot
Endothelial Cell Migration During Angiogenesis
Circ. Res., March 30, 2007; 100(6): 782 - 794.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2006 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.