Activin receptor type IIB (ActR-IIB) (ActR-IIB)

The Activin receptor type IIB (ActR-IIB) is a high-affinity cell-surface receptor belonging to the transforming growth factor-beta (TGF-β) superfamily [UniProt P27037]. It functions by binding various ligands, most notably activins, myostatin (GDF8), and GDF11, to initiate intracellular signaling through the SMAD2/3 pathway [PubMed: 24633320]. This complex is a vital regulator of physiological processes such as skeletal muscle growth, bone homeostasis, and the late stages of erythropoiesis [FDA: Reblozyl Label]. Dysregulation of Activin–ActR-IIB signaling is implicated in several pathological conditions, including muscle wasting syndromes, cancer cachexia, and certain types of anemia like beta-thalassemia [PubMed: 31745259]. In pulmonary arterial hypertension, imbalanced signaling through this receptor pathway contributes to pathological vascular remodeling [Nature Medicine: 2021, 27(7)]. Pharmacological intervention typically involves the use of soluble receptor fusion proteins, known as ligand traps, which sequester ligands before they can bind the membrane-bound receptor [PubMed: 32075889]. Additionally, monoclonal antibodies like bimagrumab have been developed to directly antagonize the receptor, aiming to increase muscle mass or treat metabolic disorders [PubMed: 24633320]. Clinical applications of these therapies have shown success in improving hemoglobin levels in patients with transfusion-dependent anemias and improving exercise capacity in pulmonary hypertension [FDA: Reblozyl Label].

Other names

ACVR2BActivin receptor type 2BActRIIBActivin A receptor type IIB

Ligand sequestration via soluble receptor decoys (ligand traps) or direct receptor antagonism by monoclonal antibodies to inhibit SMAD2/3 signaling.