Bass, M.D. orcid.org/0000-0002-8854-9705, Morgan, M.R., Roach, K.A. et al. (3 more authors) (2008) p190RhoGAP is the convergence point of adhesion signals from alpha 5 beta 1 integrin and syndecan-4. Journal of Cell Biology, 181 (6). pp. 1013-1026. ISSN 0021-9525
Abstract
The fibronectin receptors alpha(5)beta(1) integrin and syndecan-4 cocluster in focal adhesions and coordinate cell migration by making individual contributions to the suppression of RhoA activity during matrix engagement. p190Rho-guanosine triphosphatase-activating protein (GAP) is known to inhibit RhoA during the early stages of cell spreading in an Src-dependent manner. This paper dissects the mechanisms of p190RhoGAP regulation and distinguishes the contributions of alpha(5)beta(1) integrin and syndecan-4. Matrix-induced tyrosine phosphorylation of p190RhoGAP is stimulated solely by engagement of alpha(5)beta(1) integrin and is independent of syndecan-4. Parallel engagement of syndecan-4 causes redistribution of the tyrosine-phosphorylated pool of p190RhoGAP between membrane and cytosolic fractions by a mechanism that requires direct activation of protein kinase C alpha by syndecan-4. Activation of both pathways is necessary for the efficient regulation of RhoA and, as a consequence, focal adhesion formation. Accordingly, we identify p190RhoGAP as the convergence point for adhesive signals mediated by alpha(5)beta(1) integrin and syndecan-4. This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2008 Bass et al. Reproduced in accordance with the publisher's self-archiving policy. CC BY-NC-SA |
Keywords: | Animals; Cell Adhesion; Cell Membrane; Cells, Cultured; DNA-Binding Proteins; Fibroblasts; Fibronectins; Focal Adhesions; GTPase-Activating Proteins; Integrin alpha5beta1; Mice; Protein Binding; Protein Kinase C-alpha; Repressor Proteins; Signal Transduction; Syndecan-4; rhoA GTP-Binding Protein |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 09 Feb 2017 16:52 |
Last Modified: | 09 Feb 2017 16:52 |
Published Version: | http://doi.org/10.1083/jcb.200711129 |
Status: | Published |
Publisher: | Rockefeller University Press |
Refereed: | Yes |
Identification Number: | 10.1083/jcb.200711129 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108261 |
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Licence: CC-BY-NC-SA 4.0