Activin receptor type-2A and Activin receptor type-2B signaling complex (ACVR2A/ACVR2B complex)

The endogenous ACVR2A/ACVR2B-containing signaling complexes are heterotetrameric receptor assemblies on the cell surface that mediate signaling for various members of the transforming growth factor-beta (TGF-β) superfamily [1, 3]. These complexes are typically composed of two type II receptors (Activin receptor type-2A or type-2B) and two type I receptors (such as ALK4 or ALK7) [1, 2]. Upon binding ligands like activins, myostatin (GDF8), or growth differentiation factor 11 (GDF11), the type II receptors phosphorylate the type I receptors, which then activate downstream SMAD2/3 or SMAD1/5/8 signaling pathways [1, 3]. These pathways are critical regulators of physiological processes including muscle mass maintenance, erythropoiesis, bone density, and vascular remodeling [1, 2, 4]. Dysregulation of these complexes, often involving an imbalance between pro-proliferative and anti-proliferative signals, is a key driver in diseases such as pulmonary arterial hypertension (PAH), anemia, and muscle wasting disorders [1, 2]. Therapeutic strategies targeting these complexes include soluble decoy receptors (ligand traps) like sotatercept and luspatercept, which sequester circulating ligands to prevent their interaction with the endogenous receptors, as well as monoclonal antibodies like bimagrumab that bind the receptors directly [1, 2, 4].

Other names

ActRIIA/ActRIIB signaling complexActivin receptor type II signaling complexACVR2A/B-containing heteromeric complexesActivin receptor type 2A and 2B complex

Ligand sequestration (trapping) to prevent receptor activation, competitive inhibition of ligand binding via monoclonal antibodies, and modulation of downstream SMAD2/3 and SMAD1/5/8 signaling pathways.