ArticleThe Journal of biological chemistry2012
Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 174 citations in OpenAlex.
- Understanding of the different roles of Noggin in the Noggin-BMP-2 and Noggin-BMP-9 dimer complexes at the molecular level.Scientific reports · 2026Article
- RKER-012, a modified ActRIIB-Fc ligand trap with BMP sparing properties, attenuates pathological features of experimental pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2026Article
- Endoglin as a BMP9 co-receptor in vascular endothelial cells: prodomain displacement and TGFBRII recruitment.Nature communications · 2025Article
- Bone morphogenetic protein (BMP)-9, a systemic homeostasis factor with diverse functions in the liver and beyond.Bioscience reports · 2025Review
- Characterizing the Microenvironment of Cerebral Arteriovenous Malformations to Test Novel Treatment Modalities.Brain sciences · 2025Review
- CryoEM structure of ALK2:BMP6 reveals distinct mechanism that allow ALK2 to interact with both BMP and activin ligands.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Developing HaloTag and SNAP-Tag Chemical Inducers of Dimerization to Probe Receptor Oligomerization and Downstream Signaling.Angewandte Chemie (International ed. in English) · 2025Article
- Molecular Basis of Interchain Disulfide Bond Formation in BMP-9 and BMP-10.Journal of molecular biology · 2025Article
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.Protein science : a publication of the Protein Society · 2025Article
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Exploring Smad5: a review to pave the way for a deeper understanding of the pathobiology of common respiratory diseases.Molecular medicine (Cambridge, Mass.) · 2024Review
- Molecular basis of interchain disulfide-bond formation in BMP-9 and BMP-10.bioRxiv : the preprint server for biology · 2024Article
- Bone regeneration using activin A/BMP2 chimera (AB204) with collagen membrane in rats with calvarial defects.Journal of periodontal & implant science · 2024Article
- Bone morphogenetic protein signalling in pulmonary arterial hypertension: revisiting the BMPRII connection.Biochemical Society transactions · 2024Review
- Article
- Large-scale phosphoproteomics reveals activation of the MAPK/GADD45β/P38 axis and cell cycle inhibition in response to BMP9 and BMP10 stimulation in endothelial cells.Cell communication and signaling : CCS · 2024Article
- Shear Stress and Sub-Femtomolar Levels of Ligand Synergize to Activate ALK1 Signaling in Endothelial Cells.Cells · 2024Article
- Article
- Specifications of the ACMG/AMP Variant Curation Guidelines for Hereditary Hemorrhagic Telangiectasia Genes-Human mutation · 2024Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activin receptor-like kinase 1 (ALK1), an endothelial cell-specific type I receptor of the TGF-β superfamily, is an important regulator of normal blood vessel development as well as pathological tumor angiogenesis. As such, ALK1 is an important therapeutic target. Thus, several ALK1-directed agents are currently in clinical trials as anti-angiogenic cancer therapeutics. Given the biological and clinical importance of the ALK1 signaling pathway, we sought to elucidate the biophysical and structural basis underlying ALK1 signaling. The TGF-β family ligands BMP9 and BMP10 as well as the three type II TGF-β family receptors ActRIIA, ActRIIB, and BMPRII have been implicated in ALK1 signaling. Here, we provide a kinetic and thermodynamic analysis of BMP9 and BMP10 interactions with ALK1 and type II receptors. Our data show that BMP9 displays a significant discrimination in type II receptor binding, whereas BMP10 does not. We also report the crystal structure of a fully assembled ternary complex of BMP9 with the extracellular domains of ALK1 and ActRIIB. The structure reveals that the high specificity of ALK1 for BMP9/10 is determined by a novel orientation of ALK1 with respect to BMP9, which leads to a unique set of receptor-ligand interactions. In addition, the structure explains how BMP9 discriminates between low and high affinity type II receptors. Taken together, our findings provide structural and mechanistic insights into ALK1 signaling that could serve as a basis for novel anti-angiogenic therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.