title: Regulation of the ALK1 ligands, BMP9 and BMP10.
abstract: Bone morphogenetic protein (BMP)9 and BMP10 are high affinity ligands for activin receptor-like kinase 1 (ALK1), a type I BMP receptor mainly expressed on vascular endothelial cells (ECs). ALK1-mediated BMP9/BMP10 signalling pathways have emerged as essential in EC biology and in angiogenesis. Several genetic mutations in the genes encoding the ligands and receptors of this pathway have been reported in two cardiovascular diseases, pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). Administration of recombinant BMP9 reverses experimental PAH in preclinical rodent models. Dalantercept, an Fc-fusion protein of the extracellular domain of ALK1 and a ligand trap for BMP9 and BMP10, is in phase II clinical trials for anti-tumour angiogenesis. Understanding the regulation of BMP9 and BMP10, at both gene and protein levels, under physiological and pathological conditions, will reveal essential information and potential novel prognostic markers for the BMP9/BMP10-targeted therapies.
authors.affiliation: The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, U.K. wl225@cam.ac.uk.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, U.K.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Salmon
authors.affiliation: The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, U.K.
authors.forename: He
authors.initials: H
authors.lastname: Jiang
authors.affiliation: The Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, U.K.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Morrell
mesh_terms: D030301:Activin Receptors, Type II / Q000378:metabolism*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: C541386:BMP10 protein, human; D019485:Bone Morphogenetic Proteins; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D008024:Ligands; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II
keywords: BMP receptor type II (BMPR-II); activin receptor-like kinase 1 (ALK1); bone morphogenetic protein 10 (BMP10); bone morphogenetic protein 9 (BMP9); endothelial cell; signal transduction