ACVR2B

ACVR2B, or activin receptor type-2B, is a member of the activin receptor family of type II transmembrane serine/threonine kinase receptors in the transforming growth factor-beta (TGF-β) superfamily. It is encoded by the ACVR2B gene in humans and is widely expressed in many tissues, including skeletal muscle and reproductive organs.

Mechanism and signaling: Upon binding ligands such as activin A or activin B—also capable of signaling with other growth factors such as myostatin (GDF8) and GDF11—the receptor forms a complex with a type I receptor, typically ALK4 (ACVR1B) or ALK7 (ACVR1C). The activated type I receptor phosphorylates SMAD2 and SMAD3, which then partner with SMAD4 and translocate to the nucleus to regulate target gene expression. This pathway is part of the broader TGF-β signaling network that controls cell growth, differentiation, and homeostasis.

Ligand binding and specificity: ACVR2B has high affinity for activin ligands and participates in signaling by myostatin and related growth factors. The ACVR2A and ACVR2B receptors have overlapping ligand specificities, providing redundancy in signaling.

Biological roles: ACVR2B contributes to development, reproductive physiology, and tissue homeostasis. In skeletal muscle, myostatin–ACVR2B signaling acts as a key negative regulator of growth; disruption of this pathway can lead to increased muscle mass in experimental models, highlighting ACVR2B as a potential target for anabolic therapies.

Clinical and research relevance: Dysregulation of activin–ACVR2B signaling is explored in muscle-wasting conditions and cachexia. Therapeutic approaches include ligand traps or antibodies aimed at inhibiting ActRII receptor signaling to promote muscle growth. ACVR2B also participates in various processes within the broader activin signaling network.

Structure: The receptor is a single-pass transmembrane protein with an extracellular ligand-binding domain, a transmembrane segment, and an intracellular serine/threonine kinase domain that mediates signaling.