Activin and Bone Morphogenetic Protein family ligands (Activin/BMP ligands)

The Activin and Bone Morphogenetic Protein (BMP) family ligands are a subset of the Transforming Growth Factor-beta (TGF-beta) superfamily of signaling proteins (Source: Morrell et al., Gene, 2013). These ligands play critical roles in regulating cell growth, differentiation, and development across various tissues, including bone, blood, and the vasculature (Source: UniProt, 2024). They exert their biological effects by binding to specific pairs of Type I and Type II serine/threonine kinase receptors, which subsequently trigger intracellular signaling through the SMAD protein pathway. Dysregulation of these ligands is implicated in numerous pathologies; for instance, an imbalance between pro-proliferative activins/GDFs and anti-proliferative BMP signaling is a hallmark of pulmonary arterial hypertension (PAH) (Source: Hoeper et al., NEJM, 2023). In therapeutic contexts, these ligands are targeted using 'ligand traps'—recombinant fusion proteins consisting of the extracellular domain of a receptor (like ActRIIA or ActRIIB) fused to an Fc domain. Drugs like sotatercept and luspatercept utilize this mechanism to sequester circulating ligands, thereby restoring signaling balance and treating conditions such as PAH and chronic anemia (Source: Merck, 2024; BMS, 2023).

Other names

TGF-beta superfamily ligandsActivinsBone Morphogenetic ProteinsGrowth and Differentiation FactorsGDFsInhibins

Ligand trapping via recombinant fusion proteins (decoy receptors) that bind circulating ligands to prevent their interaction with endogenous cell-surface receptors and subsequent SMAD signaling (Source: Hoeper et al., NEJM, 2023).