Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells

ALK1 is an endothelial-specific type I receptor of the TGFbeta receptor family whose heterozygous mutations cause hereditary hemorrhagic telangiectasia type 2. Although TGFbeta1 and TGFbeta3 have been shown to bind ALK1 under specific experimental conditions, they may not represent the physiological ligands for this receptor. In the present study, we demonstrate that BMP9 induces the phosphorylation of Smad1/5/8 in microvascular endothelial cells, and this phosphorylation lasts over a period of 24 hours. BMP9 also activates the ID1 promoter-derived BMP response element (BRE) in a dose-dependent manner (EC50 = 45 +/- 27 pg/mL), and this activation is abolished by silencing ALK1 expression or addition of ALK1…

• LI
  Ludwig Institute for Cancer Research
• IN
  Institut National de la Santé et de la Recherche Médicale
• LU
  Leids Universitair Medisch Centrum