| First Author | Perez VA | Year | 2011 |
| Journal | J Cell Biol | Volume | 192 |
| Issue | 1 | Pages | 171-88 |
| PubMed ID | 21220513 | Mgi Jnum | J:167840 |
| Mgi Id | MGI:4880803 | Doi | 10.1083/jcb.201008060 |
| Citation | de Jesus Perez VA, et al. (2011) BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways. J Cell Biol 192(1):171-88 |
| abstractText | We present a novel cell-signaling paradigm in which bone morphogenetic protein 2 (BMP-2) consecutively and interdependently activates the wingless (Wnt)-beta-catenin (betaC) and Wnt-planar cell polarity (PCP) signaling pathways to facilitate vascular smooth muscle motility while simultaneously suppressing growth. We show that BMP-2, in a phospho-Akt-dependent manner, induces betaC transcriptional activity to produce fibronectin, which then activates integrin-linked kinase 1 (ILK-1) via alpha4-integrins. ILK-1 then induces the Wnt-PCP pathway by binding a proline-rich motif in disheveled (Dvl) and consequently activating RhoA-Rac1-mediated motility. Transfection of a Dvl mutant that binds betaC without activating RhoA-Rac1 not only prevents BMP-2-mediated vascular smooth muscle cell motility but promotes proliferation in association with persistent betaC activity. Interfering with the Dvl-dependent Wnt-PCP activation in a murine stented aortic graft injury model promotes extensive neointima formation, as shown by optical coherence tomography and histopathology. We speculate that, in response to injury, factors that subvert BMP-2-mediated tandem activation of Wnt-betaC and Wnt-PCP pathways contribute to obliterative vascular disease in both the systemic and pulmonary circulations. |
