QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 18, Issue 1, 253-264, January 2007

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-03-0207v1 18/1/253    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chang, F. Articles by Romer, L. H. Search for Related Content PubMed PubMed Citation Articles by Chang, F. Articles by Romer, L. H.

FAK Potentiates Rac1 Activation and Localization to Matrix Adhesion Sites: A Role for PIX

Fumin Chang^*, Christopher A. Lemmon^*,, Dongeun Park, and Lewis H. Romer^*,,||

Departments of *Anesthesiology and Critical Care Medicine, Biomedical Engineering, Cell Biology, and ^||Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287; and School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea

Submitted March 17, 2006; Revised October 25, 2006; Accepted October 27, 2006
Monitoring Editor: Carole Parent

FAK, a cytoplasmic protein tyrosine kinase, is activated and localized to focal adhesions upon cell attachment to extracellular matrix. FAK null cells spread poorly and exhibit altered focal adhesion turnover. Rac1 is a member of the Rho-family GTPases that promotes membrane ruffling, leading edge extension, and cell spreading. We investigated the activation and subcellular location of Rac1 in FAK null and FAK reexpressing fibroblasts. FAK reexpressers had a more robust pattern of Rac1 activation after cell adhesion to fibronectin than the FAK null cells. Translocation of Rac1 to focal adhesions was observed in FAK reexpressers, but seldom in FAK null cells. Experiments with constitutively active L61Rac1 and dominant negative N17Rac1 indicated that the activation state of Rac1 regulated its localization to focal adhesions. We demonstrated that FAK tyrosine-phosphorylated PIX and thereby increased its binding to Rac1. In addition, PIX facilitated the targeting of activated Rac1 to focal adhesions and the efficiency of cell spreading. These data indicate that FAK has a role in the activation and focal adhesion translocation of Rac1 through the tyrosine phosphorylation of PIX.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-03-0207) on November 8, 2006.

Address correspondence to: Lewis Romer (Lromer{at}jhmi.edu)

This article has been cited by other articles:

				Y. Kim, Y.-S. Lee, J. Choe, H. Lee, Y.-M. Kim, and D. Jeoung CD44-Epidermal Growth Factor Receptor Interaction Mediates Hyaluronic Acid-promoted Cell Motility by Activating Protein Kinase C Signaling Involving Akt, Rac1, Phox, Reactive Oxygen Species, Focal Adhesion Kinase, and MMP-2 J. Biol. Chem., August 15, 2008; 283(33): 22513 - 22528. [Abstract] [Full Text] [PDF]

				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]

				K.-A. Nakrieko, I. Welch, H. Dupuis, D. Bryce, A. Pajak, R. St. Arnaud, S. Dedhar, S. J. A. D'Souza, and L. Dagnino Impaired Hair Follicle Morphogenesis and Polarized Keratinocyte Movement upon Conditional Inactivation of Integrin-linked Kinase in the Epidermis Mol. Biol. Cell, April 1, 2008; 19(4): 1462 - 1473. [Abstract] [Full Text] [PDF]

				M. W. Mayhew, E. D. Jeffery, N. E. Sherman, K. Nelson, J. M. Polefrone, S. J. Pratt, J. Shabanowitz, J. T. Parsons, J. W. Fox, D. F. Hunt, et al. Identification of phosphorylation sites in betaPIX and PAK1 J. Cell Sci., November 15, 2007; 120(22): 3911 - 3918. [Full Text] [PDF]

				N. Hoshina, T. Tezuka, K. Yokoyama, H. Kozuka-Hata, M. Oyama, and T. Yamamoto Focal adhesion kinase regulates laminin-induced oligodendroglial process outgrowth. Genes Cells, November 1, 2007; 12(11): 1245 - 1254. [Abstract] [Full Text] [PDF]

				T. Nagy, H. Wei, T.-L. Shen, X. Peng, C.-C. Liang, B. Gan, and J.-L. Guan Mammary Epithelial-specific Deletion of the Focal Adhesion Kinase Gene Leads to Severe Lobulo-Alveolar Hypoplasia and Secretory Immaturity of the Murine Mammary Gland J. Biol. Chem., October 26, 2007; 282(43): 31766 - 31776. [Abstract] [Full Text] [PDF]