Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its
orphan domain, inhibits blood vessel formation, and suppresses tumor growth
Endoglin (CD105), a transmembrane protein of the transforming growth
factor β superfamily, plays a crucial role in angiogenesis. Mutations
in endoglin result in the vascular defect known as hereditary
hemorrhagic telangiectasia (HHT1). The soluble form of endoglin was
suggested to contribute to the pathogenesis of preeclampsia. To obtain
further insight into its function, we cloned, expressed, purified, and
characterized the extracellular domain (ECD) of mouse and human
endoglin fused to an immunoglobulin Fc domain. We found that mouse and
human endoglin ECD-Fc bound directly, specifically, and with high
affinity to bone morphogenetic proteins 9 and 10 (BMP9 AND BMP10)
in surface plasmon resonance (Biacore) and cell-based assays. We
performed a function mapping analysis of the different domains of
endoglin by examining their contributions to the selectivity and
biological activity of the protein. The BMP9/BMP10 binding
site was localized to the orphan domain of human endoglin composed of
the amino acid sequence 26-359. We established that endoglin and type
II receptors bind to overlapping sites on BMP9. In the in vivo chick
chorioallantoic membrane assay, the mouse and the truncated human
endoglin ECD-Fc both significantly reduced VEGF-induced vessel
formation. Finally, murine endoglin ECD-Fc acted as an anti-angiogenic
factor that decreased blood vessel sprouting in VEGF/FGF-induced
angiogenesis in in vivo angioreactors and reduced the tumor burden in
the colon-26 mouse tumor model. Together our findings indicate an
important role of soluble endoglin ECD in the regulation of
angiogenesis and highlight efficacy of endoglin-Fc as a potential
anti-angiogenesis therapeutic agent.
Castonguay R, et al. J Biol Chem. 2011 Aug 26;286(34):30034-46. Epub 2011 Jul 7
Human BMP-10 (mature form)
Code No.: 00005-01-100
Size: 100 ug
Price: $360.00 USD
Protein ID:O95393
Gene ID: 27302
MW:14.8KD
Tag: His Tag on N-Terminus
Expressed: E. Coli
Purity: 95%
Data Sheet: PDF