Activin receptor type IIA (ACVR2A) (ACVR2A)

Activin receptor type IIA (ACVR2A) is a transmembrane serine/threonine kinase receptor that mediates signaling for a subset of the transforming growth factor-beta (TGF-beta) superfamily ligands, including activins and growth differentiation factors (GDFs) [UniProt: P27037]. Upon ligand binding, ACVR2A forms a complex with type I receptors to activate the Smad2/3 intracellular signaling pathway, which is a critical regulator of cell proliferation, differentiation, and tissue homeostasis [PubMed: 33055117]. In diseases such as pulmonary arterial hypertension (PAH), an imbalance between Smad2/3 and Smad1/5/8 signaling leads to pathological vascular remodeling and increased pulmonary arterial pressure [NEJM: 384.15]. Therapeutic intervention targeting this axis involves the use of ligand traps, such as sotatercept, which consist of the extracellular domain of ACVR2A fused to an Fc fragment [Lancet: 397.10293]. These agents sequester circulating ligands to restore signaling balance, effectively reducing pulmonary vascular resistance in PAH and improving erythropoiesis in hematologic disorders like myelodysplastic syndromes [Blood: 136.22]. Safety monitoring for these therapies typically focuses on hemoglobin levels and blood pressure due to the receptor's role in red blood cell production and vascular tone.

Other names

ACTRIIACVR2Activin A receptor type IIAType II activin receptorACVR2A

Ligand trap mechanism where a soluble fusion protein (e.g., ACVR2A-Fc) binds and sequesters circulating TGF-beta superfamily ligands (Activin A, GDF8, GDF11), preventing them from activating the cell-surface Activin receptor type IIA and thereby inhibiting the Smad2/3 signaling pathway.