Activin receptor-like kinase 1 and bone morphogenetic protein receptor type 2 receptor complex (ALK1/BMPR2 receptor complex)

The ALK1/BMPR2 receptor complex refers to a heterotetrameric assembly of transmembrane serine/threonine kinase receptors, typically formed upon binding of bone morphogenetic protein (BMP) ligands (notably BMP9 or BMP10) to the high-affinity type I receptor ALK1 (Activin receptor-like kinase 1) and the type II receptor BMPR2 (Bone morphogenetic protein receptor type 2). Both ALK1 and BMPR2 are single-pass transmembrane proteins with extracellular ligand-binding domains and intracellular kinase domains. Upon BMP ligand engagement, the receptors oligomerize, enabling BMPR2 to phosphorylate and activate ALK1, which in turn phosphorylates downstream SMAD1/5/8 transcription factors. This initiates a transcriptional program critical for maintenance of endothelial cell function and vascular homeostasis. Pathogenic mutations in BMPR2 disrupt this process and are the primary genetic cause of hereditary pulmonary arterial hypertension, while ALK1 mutations cause hereditary hemorrhagic telangiectasia. The ALK1/BMPR2 receptor complex is an actively investigated therapeutic target in vascular diseases and oncology, owing to its central role in angiogenic and homeostatic vascular signaling.

Other names

ALK1–BMPR2 receptor complexActivin receptor-like kinase 1/BMPR2 signaling complexACVRL1/BMPR2 complexBMP type I and type II receptor complex

Drugs targeting this complex typically inhibit or modulate BMP ligand binding, receptor assembly, or downstream SMAD phosphorylation and transcriptional responses.