The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells
Abstract
ALK1 is an endothelial-specific type I receptor of the TGFβ receptor family whose heterozygous mutations cause hereditary hemorrhagic telangiectasia type 2. Although TGFβ1 and TGFβ3 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 extracellular domain. Overexpression of endoglin increases the BMP9 response, whereas silencing of both BMPRII and ActRIIA expressions completely abolishes it. BMP10, which is structurally close to BMP9, is also a potent ALK1 ligand. Finally, we demonstrate that BMP9 and BMP10 potently inhibit endothelial cell migration and growth, and stimulate endothelial expression of a panel of genes that was previously reported to be activated by the constitutively active form of ALK1. Taken together, our results suggest that BMP9 and BMP10 are two specific ALK1 ligands that may physiologically trigger the effects of ALK1 on angiogenesis.
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Cites
Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus
Shi, Y., & Massagué, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00432-x · Cited by 5,857
Smad-dependent and Smad-independent pathways in TGF-β family signalling
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Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors
Goumans, M.-J. (2002) · The EMBO Journal · doi:10.1093/emboj/21.7.1743 · Cited by 1,123
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Activin Receptor-like Kinase (ALK)1 Is an Antagonistic Mediator of Lateral TGFβ/ALK5 Signaling
Goumans, M.-J., Valdimarsdottir, G., Itoh, S., Lebrin, F., Larsson, J., Mummery, C., Karlsson, S., & ten Dijke, P. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00386-1 · Cited by 689
Endoglin promotes endothelial cell proliferation and TGF‐β/ALK1 signal transduction
Lebrin, F., Goumans, M., Jonker, L., Carvalho, R. L., Valdimarsdottir, G., Thorikay, M., Mummery, C., Arthur, H. M., & Dijke, P. T. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600386 · Cited by 652
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Cited by
TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology
Morikawa, M., Derynck, R., & Miyazono, K. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a021873 · Cited by 1,321
Cellular and Molecular Basis of Pulmonary Arterial Hypertension
Morrell, N. W., Adnot, S., Archer, S. L., Dupuis, J., Lloyd Jones, P., MacLean, M. R., McMurtry, I. F., Stenmark, K. R., Thistlethwaite, P. A., Weissmann, N., et al. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.04.018 · Cited by 819
Signaling Receptors for TGF-β Family Members
Heldin, C.-H., & Moustakas, A. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022053 · Cited by 711
Bone morphogenetic proteins: a critical review
Bragdon, B., Moseychuk, O., Saldanha, S., King, D., Julian, J., & Nohe, A. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2010.10.003 · Cited by 691
Sotatercept for the Treatment of Pulmonary Arterial Hypertension
Humbert, M., McLaughlin, V., Gibbs, J. S. R., Gomberg-Maitland, M., Hoeper, M. M., Preston, I. R., Souza, R., Waxman, A., Escribano Subias, P., Feldman, J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2024277 · Cited by 608
Metadata
- Authors
- David, L., Mallet, C., Mazerbourg, S., Feige, J.-J., & Bailly, S.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-10-26
- Volume
- 109
- Issue
- 5
- Pages
- 1953-1961
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2093316809
- Cited by
- 708
- References
- 42
- FWCI
- 9.82
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. https://app.cochat.ai/papers/10.1182/blood-2006-07-034124
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- David, L., Mallet, C., Mazerbourg, S., Feige, J.-J., & Bailly, S. (2007). Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood. https://doi.org/10.1182/blood-2006-07-034124
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