spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 15 July 2003
doi: 10.1242/jcs.00663

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.00663v1
116/17/3543    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Russell, A. J.
Right arrow Articles by Marinkovich, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Russell, A. J.
Right arrow Articles by Marinkovich, M. P.
Journal of Cell Science 116, 3543-3556 (2003)
doi: 10.1242/jcs.00663

Research Article

{alpha}6ß4 integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of {alpha}3ß1 integrin

Alan J. Russell1,*, Edgar F. Fincher1, Linda Millman1, Robyn Smith1, Veronica Vela1, Elizabeth A. Waterman1, Clara N. Dey1, Shireen Guide1, Valerie M. Weaver2 and M. Peter Marinkovich1,{ddagger}

1 Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
2 Pathology & Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

{ddagger} Author for correspondence (e-mail: mpm{at}stanford.edu)

Accepted 12 May 2003

Growth factor-induced cell migration and proliferation are essential for epithelial wound repair. Cell migration during wound repair also depends upon expression of laminin-5, a ligand for {alpha}6ß4 integrin. We investigated the role of {alpha}6ß4 integrin in laminin-5-dependent keratinocyte migration by re-expressing normal or attachment-defective ß4 integrin in ß4 integrin null keratinocytes. We found that expression of ß4 integrin in either a ligand bound or ligand unbound state was necessary and sufficient for EGF-induced cell migration. In a ligand bound state, ß4 integrin supported EGF-induced cell migration though sustained activation of Rac1. In the absence of {alpha}6ß4 integrin ligation, Rac1 activation became tempered and EGF chemotaxis proceeded through an alternate mechanism that depended upon {alpha}3ß1 integrin and was characterized by cell scattering. {alpha}3ß1 integrin also relocalated from cell-cell contacts to sites of basal clustering where it displayed increased conformational activation. The aberrant distribution and activation of {alpha}3ß1 integrin in attachment-defective ß4 cells could be reversed by the activation of Rac1. Conversely, in WT ß4 cells the normal cell-cell localization of {alpha}3ß1 integrin became aberrant after the inhibition of Rac1. These studies indicate that the extracellular domain of ß4 integrin, through its ability to bind ligand, functions to integrate the divergent effects of growth factors on the cytoskeleton and adhesion receptors so that coordinated keratinocyte migration can be achieved.

Key words: {alpha}6ß4 Integrin, EGF, Laminin-5, Keratinocyte, Chemotaxis




This article has been cited by other articles:


Home page
 Cancer Res.Home page
M. Tran, P. Rousselle, P. Nokelainen, S. Tallapragada, N. T. Nguyen, E. F. Fincher, and M. P. Marinkovich
Targeting a Tumor-Specific Laminin Domain Critical for Human Carcinogenesis
Cancer Res., April 15, 2008; 68(8): 2885 - 2894.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
S. Taboubi, J. Milanini, E. Delamarre, F. Parat, F. Garrouste, G. Pommier, J. Takasaki, J.-C. Hubaud, H. Kovacic, and M. Lehmann
G{alpha}(q/11)-coupled P2Y2 nucleotide receptor inhibits human keratinocyte spreading and migration
FASEB J, December 1, 2007; 21(14): 4047 - 4058.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
N. S. Tan, G. Icre, A. Montagner, B. B.-t. Heggeler, W. Wahli, and L. Michalik
The Nuclear Hormone Receptor Peroxisome Proliferator-Activated Receptor {beta}/{delta} Potentiates Cell Chemotactism, Polarization, and Migration
Mol. Cell. Biol., October 15, 2007; 27(20): 7161 - 7175.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J. C. Friedland, J. N. Lakins, M. G. Kazanietz, J. Chernoff, D. Boettiger, and V. M. Weaver
{alpha}6beta4 integrin activates Rac-dependent p21-activated kinase 1 to drive NF-{kappa}B-dependent resistance to apoptosis in 3D mammary acini
J. Cell Sci., October 15, 2007; 120(20): 3700 - 3712.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. A. Waterman, N. Sakai, N. T. Nguyen, B. A.J. Horst, D. P. Veitch, C. N. Dey, S. Ortiz-Urda, P. A. Khavari, and M. P. Marinkovich
A Laminin-Collagen Complex Drives Human Epidermal Carcinogenesis through Phosphoinositol-3-Kinase Activation
Cancer Res., May 1, 2007; 67(9): 4264 - 4270.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. E. Werner, F. Chen, J. V. Moyano, F. Yehiely, J. C. R. Jones, and V. L. Cryns
Caspase Proteolysis of the Integrin beta4 Subunit Disrupts Hemidesmosome Assembly, Promotes Apoptosis, and Inhibits Cell Migration
J. Biol. Chem., February 23, 2007; 282(8): 5560 - 5569.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. U. Sehgal, P. J. DeBiase, S. Matzno, T.-L. Chew, J. N. Claiborne, S. B. Hopkinson, A. Russell, M. P. Marinkovich, and J. C. R. Jones
Integrin beta4 Regulates Migratory Behavior of Keratinocytes by Determining Laminin-332 Organization
J. Biol. Chem., November 17, 2006; 281(46): 35487 - 35498.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
C. E. Pullar, B. S. Baier, Y. Kariya, A. J. Russell, B. A.J. Horst, M. P. Marinkovich, and R. R. Isseroff
beta4 Integrin and Epidermal Growth Factor Coordinately Regulate Electric Field-mediated Directional Migration via Rac1
Mol. Biol. Cell, November 1, 2006; 17(11): 4925 - 4935.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
T. C. Sroka, M. E. Pennington, and A. E. Cress
Synthetic D-amino acid peptide inhibits tumor cell motility on laminin-5
Carcinogenesis, September 1, 2006; 27(9): 1748 - 1757.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
E. Natarajan, J. D. Omobono II, Z. Guo, S. Hopkinson, A. J.F. Lazar, T. Brenn, J. C. Jones, and J. G. Rheinwald
A Keratinocyte Hypermotility/Growth-Arrest Response Involving Laminin 5 and p16INK4A Activated in Wound Healing and Senescence
Am. J. Pathol., June 1, 2006; 168(6): 1821 - 1837.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. Wilhelmsen, S. H.M. Litjens, and A. Sonnenberg
Multiple Functions of the Integrin {alpha}6{beta}4 in Epidermal Homeostasis and Tumorigenesis
Mol. Cell. Biol., April 15, 2006; 26(8): 2877 - 2886.
[Full Text] [PDF]

Home page
 J. Cell Sci.Home page
N. T. Chartier, M. Laine, S. Gout, G. Pawlak, C. A. Marie, P. Matos, M. R. Block, and M. R. Jacquier-Sarlin
Laminin-5-integrin interaction signals through PI 3-kinase and Rac1b to promote assembly of adherens junctions in HT-29 cells
J. Cell Sci., January 1, 2006; 119(1): 31 - 46.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. N. Nikolopoulos, P. Blaikie, T. Yoshioka, W. Guo, C. Puri, C. Tacchetti, and F. G. Giancotti
Targeted Deletion of the Integrin {beta}4 Signaling Domain Suppresses Laminin-5-Dependent Nuclear Entry of Mitogen-Activated Protein Kinases and NF-{kappa}B, Causing Defects in Epidermal Growth and Migration
Mol. Cell. Biol., July 15, 2005; 25(14): 6090 - 6102.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Hintermann, N. Yang, D. O'Sullivan, J. M. G. Higgins, and V. Quaranta
Integrin {alpha}6{beta}4-erbB2 Complex Inhibits Haptotaxis by Up-regulating E-cadherin Cell-Cell Junctions in Keratinocytes
J. Biol. Chem., March 4, 2005; 280(9): 8004 - 8015.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
D. P. Choma, K. Pumiglia, and C. M. DiPersio
Integrin {alpha}3{beta}1 directs the stabilization of a polarized lamellipodium in epithelial cells through activation of Rac1
J. Cell Sci., August 1, 2004; 117(17): 3947 - 3959.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
M. Bruewer, A. M. Hopkins, M. E. Hobert, A. Nusrat, and J. L. Madara
RhoA, Rac1, and Cdc42 exert distinct effects on epithelial barrier via selective structural and biochemical modulation of junctional proteins and F-actin
Am J Physiol Cell Physiol, August 1, 2004; 287(2): C327 - C335.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
N. Zahir, J. N. Lakins, A. Russell, W. Ming, C. Chatterjee, G. I. Rozenberg, M. P. Marinkovich, and V. M. Weaver
Autocrine laminin-5 ligates {alpha}6{beta}4 integrin and activates RAC and NF{kappa}B to mediate anchorage-independent survival of mammary tumors
J. Cell Biol., December 22, 2003; 163(6): 1397 - 1407.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2003