Activin receptor type-2B–containing bone morphogenetic protein receptor complex (ACVR2B–BMPR complex)

Activin receptor type-2B (ACVR2B)–containing bone morphogenetic protein (BMP) receptor complexes are heteromeric signaling units composed of the type II receptor ACVR2B and various type I receptors, such as ALK2, ALK3, or ALK6 (Wikipedia, 2024; Hella et al., 2015). These complexes serve as critical mediators for a broad range of ligands within the TGF-beta superfamily, including BMPs, activins, myostatin, and growth differentiation factor 11 (GDF11) (NIH, 2017; Maayanlab, 2024). Upon ligand binding, the constitutively active kinase domain of ACVR2B phosphorylates the type I receptor, which subsequently activates intracellular SMAD transcription factors (SMAD1/5/8 or SMAD2/3) to regulate biological processes such as erythropoiesis, bone formation, and skeletal muscle growth (UniProt, 2024; Hella et al., 2015). In various disease states, the balance of signaling through these complexes is disrupted; for example, overactive signaling by GDF11 and activins through ACVR2B-containing complexes can impair red blood cell maturation, leading to chronic anemia in conditions like myelodysplastic syndromes and beta-thalassemia (Maayanlab, 2024; NIH, 2017). Consequently, these complexes and their ligands have become major therapeutic targets. Drugs like luspatercept act as ligand traps by using a modified extracellular domain of ACVR2B to sequester inhibitory ligands, thereby restoring effective erythropoiesis (Maayanlab, 2024). Additionally, monoclonal antibodies like bimagrumab target the ACVR2B receptor directly to promote muscle growth in wasting disorders, highlighting the complex's pivotal role in regenerative medicine and hematology (Patsnap, 2024; Maayanlab, 2024).

Other names

ACVR2B–BMP receptor complexActRIIB–BMP receptor complexActivin receptor type IIB–containing BMP receptor complexACVR2B–ALK2 complexACVR2B–ALK3 complex

Ligand trapping (sequestration of TGF-beta superfamily ligands such as GDF11, Activin A, and Myostatin) and receptor antagonism (direct binding to ACVR2B to block ligand-induced signaling).