Am J Physiol Cell Physiol Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Am J Physiol Cell Physiol 294: C931-C944, 2008. First published January 23, 2008; doi:10.1152/ajpcell.00359.2007
0363-6143/08 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
294/4/C931    most recent
00359.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Herrera Abreu, M. T.
Right arrow Articles by Downey, G. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Herrera Abreu, M. T.
Right arrow Articles by Downey, G. P.

EXTRACELLULAR MATRIX, CELL INTERACTIONS

Tyrosine phosphatase PTP{alpha} regulates focal adhesion remodeling through Rac1 activation

Maria Teresa Herrera Abreu,1 Patricia Castellanos Penton,1 Vivian Kwok,1 Eric Vachon,1 David Shalloway,2 Luis Vidali,3 Wilson Lee,4 Christopher A. McCulloch,4 and Gregory P. Downey1

1Division of Respirology, Department of Medicine, and 4Canadian Institutes of Health Research Group in Matrix Dynamics, Faculty of Dentistry, University of Toronto and Toronto General Hospital Research Institute of the University Health Network, Toronto, Ontario, Canada; 2Cornell University, Ithaca, New York; and 3Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts

Submitted 10 August 2007 ; accepted in final form 18 January 2008

We characterized the role of protein tyrosine phosphatase (PTP)-{alpha} in focal adhesion (FA) formation and remodeling using wild-type and PTP{alpha}-deficient (PTP{alpha}–/–) cells. Compared with wild-type cells, spreading PTP{alpha}–/– fibroblasts displayed fewer leading edges and formed elongated {alpha}-actinin-enriched FA at the cell periphery. These features suggest the presence of slowly remodeling cell adhesions and were phenocopied in human fibroblasts in which PTP{alpha} was knocked down using short interfering RNA (siRNA) or in NIH-3T3 fibroblasts expressing catalytically inactive (C433S/C723S) PTP{alpha}. Fluorescence recovery after photobleaching showed slower green fluorescence protein-{alpha}-actinin recovery in the FA of PTP{alpha}–/– than wild-type cells. These alterations correlated with reduced cell spreading, adhesion, and polarization and retarded contraction of extracellular matrices in PTP{alpha}–/– fibroblasts. Activation of Rac1 and its recruitment to FA during spreading were diminished in cells expressing C433S/C723S PTP{alpha}. Rac1–/– cells also displayed abnormally elongated and peripherally distributed FA that failed to remodel. Conversely, expression of constitutively active Rac1 restored normal FA remodeling in PTP{alpha}–/– cells. We conclude that PTP{alpha} is required for remodeling of FA during cell spreading via a pathway involving Rac1.

cell spreading; integrins; extracellular matrix; actin cytoskeleton



Address for reprint requests and other correspondence: G. P. Downey, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206 (e-mail: downeyg{at}njc.org)







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2008 by the American Physiological Society.