Abstract
Cell migration during vascular remodelling is regulated by crosstalk between growth factor receptors and integrin receptors, which together coordinate cytoskeletal and motogenic changes. Here, we report extracellular matrix (ECM)-directed crosstalk between platelet-derived growth factor receptor (PDGFR)-β and α5β 1-integrin, which controls the migration of mesenchymal stem (stromal) cells (MSCs). Cell adhesion to fibronectin induced α5β -integrin-dependent phosphorylation of PDGFR-β in the absence of growth factor stimulation. Phosphorylated PDGFR-β co-immunoprecipitated with α5-integrin and colocalised with a5b1-integrin in the transient tidemarks of focal adhesions. Adhesion to fibronectin also strongly potentiated PDGF-BB-induced PDGFR-b phosphorylation and focal adhesion kinase (FAK) activity, in an a5b1-integrin-dependent manner. PDGFR-b-induced phosphoinositide 3-kinase (PI3K) and Akt activity, actin reorganisation and cell migration were all regulated by fibronectin and a5b1-integrin. This synergistic relationship between a5b1-integrin and PDGFR-b is a fundamental determinant of cell migration. Thus, fibronectin-rich matrices can prime PDGFR-b to recruit mesenchymal cells at sites of vascular remodelling. © 2011. Published by The Company of Biologists Ltd.
Original language | English |
---|---|
Pages (from-to) | 1288-1300 |
Number of pages | 12 |
Journal | Journal of Cell Science |
Volume | 124 |
Issue number | 8 |
DOIs | |
Publication status | Published - 15 Apr 2011 |
Keywords
- A5b1-Integrin
- Fibronectin
- Mesenchymal stem cell
- Migration
- Platelet-derived growth factor receptor-b
- Signalling