| First Author | Zhu Q | Year | 2013 |
| Journal | J Cell Biol | Volume | 202 |
| Issue | 6 | Pages | 937-50 |
| PubMed ID | 24019535 | Mgi Jnum | J:201739 |
| Mgi Id | MGI:5515651 | Doi | 10.1083/jcb.201208113 |
| Citation | Zhu Q, et al. (2013) SnoN facilitates ALK1-Smad1/5 signaling during embryonic angiogenesis. J Cell Biol 202(6):937-50 |
| abstractText | In endothelial cells, two type I receptors of the transforming growth factor beta (TGF-beta) family, ALK1 and ALK5, coordinate to regulate embryonic angiogenesis in response to BMP9/10 and TGF-beta. Whereas TGF-beta binds to and activates ALK5, leading to Smad2/3 phosphorylation and inhibition of endothelial cell proliferation and migration, BMP9/10 and TGF-beta also bind to ALK1, resulting in the activation of Smad1/5. SnoN is a negative regulator of ALK5 signaling through the binding and repression of Smad2/3. Here we uncover a positive role of SnoN in enhancing Smad1/5 activation in endothelial cells to promote angiogenesis. Upon ligand binding, SnoN directly bound to ALK1 on the plasma membrane and facilitated the interaction between ALK1 and Smad1/5, enhancing Smad1/5 phosphorylation. Disruption of this SnoN-Smad interaction impaired Smad1/5 activation and up-regulated Smad2/3 activity. This resulted in defective angiogenesis and arteriovenous malformations, leading to embryonic lethality at E12.5. Thus, SnoN is essential for TGF-beta/BMP9-dependent biological processes by its ability to both positively and negatively modulate the activities of Smad-dependent pathways. |
