Title

Snon facilitates alk1-smad1/5 signaling duringembryonic angiogenesis

Document Type

Article

Abstract

n endothelial cells, two type I receptors of the transforming growth factor ? (TGF-β) family, ALK1 and ALK5, coordinate to regulate embryonic angiogenesis in response to BMP9/10 and TGF-β. Whereas TGF-β binds to and activates ALK5, leading to Smad2/3 phosphorylation and inhibition of endothelial cell proliferation and migration, BMP9/10 and TGF-β 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-β/BMP9-dependent biological processes by its ability to both positively and negatively modulate the activities of Smad-dependent pathways.©2013 Zhu et al.

Publication Date

9-25-2013

Publication Title

Journal of Cell Biology

ISSN

00219525

E-ISSN

15408140

Volume

202

Issue

6

First Page

937

Last Page

950

PubMed ID

24019535

Digital Object Identifier (DOI)

10.1083/jcb.201208113

This document is currently not available here.

Share

COinS