| First Author | Curado F | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 24 | Pages | 4389-403 |
| PubMed ID | 25266657 | Mgi Jnum | J:224324 |
| Mgi Id | MGI:5662024 | Doi | 10.1128/MCB.01026-14 |
| Citation | Curado F, et al. (2014) ALK5 and ALK1 play antagonistic roles in transforming growth factor beta-induced podosome formation in aortic endothelial cells. Mol Cell Biol 34(24):4389-403 |
| abstractText | Transforming growth factor beta (TGF-beta) and related cytokines play a central role in the vascular system. In vitro, TGF-beta induces aortic endothelial cells to assemble subcellular actin-rich structures specialized for matrix degradation called podosomes. To explore further this TGF-beta-specific response and determine in which context podosomes form, ALK5 and ALK1 TGF-beta receptor signaling pathways were investigated in bovine aortic endothelial cells. We report that TGF-beta drives podosome formation through ALK5 and the downstream effectors Smad2 and Smad3. Concurrent TGF-beta-induced ALK1 signaling mitigates ALK5 responses through Smad1. ALK1 signaling induced by BMP9 also antagonizes TGF-beta-induced podosome formation, but this occurs through both Smad1 and Smad5. Whereas ALK1 neutralization brings ALK5 signals to full potency for TGF-beta-induced podosome formation, ALK1 depletion leads to cell disturbances not compatible with podosome assembly. Thus, ALK1 possesses passive and active modalities. Altogether, our results reveal specific features of ALK1 and ALK5 signaling with potential clinical implications. |
