HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 22, 23510-23516, May 28, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/22/23510    most recent M402169200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barker, T. H. Articles by Hagood, J. S. Search for Related Content PubMed PubMed Citation Articles by Barker, T. H. Articles by Hagood, J. S. Social Bookmarking                      What's this?

Thrombospondin-1-induced Focal Adhesion Disassembly in Fibroblasts Requires Thy-1 Surface Expression, Lipid Raft Integrity, and Src Activation^*

Thomas H. Barker, Manuel A. Pallero¶||, Mark W. MacEwen**, Samuel G. Tilden**, Anne Woods||, Joanne E. Murphy-Ullrich¶||, and James S. Hagood||**

From the Department of Biomedical Engineering, School of Engineering, ^¶Department of Pathology, Division of Molecular and Cellular Pathology, Departments of ^**Pediatrics (Pulmonary Division) and Cell Biology, the ^||Cell Adhesion and Matrix Research Center, and the Biomedical Implant Center, University of Alabama at Birmingham, Birmingham, Alabama 35294

The hep I peptide of thrombospondin-1 is known to induce the disassembly of focal adhesions, a critical step in regulating cellular adhesive changes needed for cell motility. Fibroblasts that are heterogeneous with respect to the surface expression of Thy-1 differ markedly in morphology, cytoskeletal organization, and migration, suggesting differential regulation of focal adhesion dynamics. Here we demonstrate that disassembly of focal adhesions mediated by both full-length thrombospondin-1 and the hep I peptide in fibroblasts requires the expression of Thy-1, although it does not appear to function as a stable member of the hep I receptor complex. Consistent with a known function of Thy-1 in regulating lipid raft-associated signaling, intact lipid rafts are necessary for hep I-mediated focal adhesion disassembly. Furthermore, we establish Src family kinase (SFK) activation as a novel component required for hep I-induced signaling leading to focal adhesion disassembly. hep I induces transient phosphorylation of SFKs in Thy-1-expressing fibroblasts only. Therefore, we conclude that Thy-1 surface expression is required for thrombospondin-1-induced focal adhesion disassembly in fibroblasts through an SFK-dependent mechanism. This represents a novel role for Thy-1 in the regulation of fibroblast-matrix interactions critical to tissue homeostasis and remodeling.

Received for publication, February 26, 2004 , and in revised form, March 15, 2004.

^* This work was supported by NASA Graduate Student Research Program Grant NGT5-50409 (to T. H. B.), NHLBI, National Institutes of Health Grant HL65348 (to J. S. H.) and NIAMS, National Institutes of Health Grants AR46378 (to J. S. H.) and P60 AR 20614 (to Dr. Robert Kimberly). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Depts. of Pediatrics and Cell Biology, 1600 7th Ave. S., University of Alabama at Birmingham, Birmingham, AL 35294-0011. Tel.: 205-975-5224; Fax: 205-975-5224; E-mail: Jhagood{at}peds.uab.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. P. Lillis, L. B. Van Duyn, J. E. Murphy-Ullrich, and D. K. Strickland LDL Receptor-Related Protein 1: Unique Tissue-Specific Functions Revealed by Selective Gene Knockout Studies Physiol Rev, July 1, 2008; 88(3): 887 - 918. [Abstract] [Full Text] [PDF]

				S. Papp, M. P. Fadel, H. Kim, C. A. McCulloch, and M. Opas Calreticulin Affects Fibronectin-based Cell-Substratum Adhesion via the Regulation of c-Src Activity J. Biol. Chem., June 1, 2007; 282(22): 16585 - 16598. [Abstract] [Full Text] [PDF]

				Y. Y. Sanders, P. Kumbla, and J. S. Hagood Enhanced Myofibroblastic Differentiation and Survival in Thy-1(-) Lung Fibroblasts Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 226 - 235. [Abstract] [Full Text] [PDF]

				T. A. Rege and J. S. Hagood Thy-1 as a regulator of cell-cell and cell-matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis FASEB J, June 1, 2006; 20(8): 1045 - 1054. [Abstract] [Full Text] [PDF]

				K. R. Stenmark, N. Davie, M. Frid, E. Gerasimovskaya, and M. Das Role of the Adventitia in Pulmonary Vascular Remodeling Physiology, April 1, 2006; 21(2): 134 - 145. [Abstract] [Full Text] [PDF]

				J. S. Hagood, P. Prabhakaran, P. Kumbla, L. Salazar, M. W. MacEwen, T. H. Barker, L. A. Ortiz, T. Schoeb, G. P. Siegal, C. B. Alexander, et al. Loss of Fibroblast Thy-1 Expression Correlates with Lung Fibrogenesis Am. J. Pathol., August 1, 2005; 167(2): 365 - 379. [Abstract] [Full Text] [PDF]