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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Roach, Kirsty A. Bass, Mark D. Settleman, Jeffrey Humphries, Martin J. Morgan, Mark R. Goryachev, Andrew B. |
| Description | Author Affiliation: Bass MD ( Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.) |
| Abstract | The fibronectin receptors $α_{5}β_{1}$ 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 $α_{5}β_{1}$ integrin and syndecan-4. Matrix-induced tyrosine phosphorylation of p190RhoGAP is stimulated solely by engagement of $α_{5}β_{1}$ 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 α 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 $α_{5}β_{1}$ integrin and syndecan-4. This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 6 |
| Volume Number | 181 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2008-06-16 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA-Binding Proteins Metabolism GTPase-Activating Proteins Integrin Alpha5beta1 Repressor Proteins Signal Transduction Syndecan-4 Animals Cell Adhesion Cell Membrane Cells, Cultured Fibroblasts Cytology Enzymology Fibronectins Focal Adhesions Mice Protein Binding Protein Kinase C-alpha RhoA GTP-Binding Protein Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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