Activin receptor type-2A (ACVR2A) (ACVR2A)

Activin receptor type-2A (ACVR2A) is a high-affinity transmembrane serine/threonine kinase receptor that belongs to the transforming growth factor-beta (TGF-beta) receptor family [UniProt: P27037]. It plays a pivotal role in mediating signals from various ligands, including activins, inhibins, and growth differentiation factors (GDFs), which are essential for regulating erythropoiesis, bone homeostasis, and reproductive functions [PubMed: 30215131]. Upon ligand binding, ACVR2A recruits and phosphorylates type-1 receptors, initiating a signaling cascade through the SMAD2/3 pathway to regulate gene expression [PubMed: 25100793]. In pathological conditions such as pulmonary arterial hypertension (PAH) and certain anemias, overactive signaling through this receptor contributes to vascular remodeling and impaired red blood cell maturation [PubMed: 32114530]. Consequently, ACVR2A has emerged as a significant therapeutic target, particularly through the development of ligand traps like sotatercept. Sotatercept is a soluble fusion protein that sequesters circulating ligands, thereby restoring the balance between pro-proliferative and anti-proliferative signaling pathways [FDA: Winrevair Label]. This therapeutic approach has demonstrated clinical success in improving exercise capacity in PAH patients and managing anemia in hematologic disorders.

Other names

Activin receptor type IIAACTRIIAACVR2ACTRIIActivin A receptor type 2A

Ligand trap mechanism where a soluble fusion protein (decoy receptor) binds circulating TGF-beta superfamily ligands (such as activins and GDFs), preventing them from activating the endogenous membrane-bound receptor and downstream SMAD signaling pathways [PubMed: 32114530].