Activin R2A

Activin proteins are involved in a wide range of biological processes including mesoderm induction, neural cell differentiation, bone remodeling, hematopoiesis, the regulation of reproductive physiology, inflammation, and carcinogenesis. They function through heteromeric complexes of type I and type II serine/threonine kinase receptors. Dimeric ligands bind to a type II receptor, such as Activin Receptor IIA (ActRIIA or activin R2A), which then associates with a type I receptor to initiate signal transduction. ActRIIA mediates the pleiotropic effects of Activins and Inhibins as well as several members of the BMP and GDF families of TGF β like proteins. Mature human ActRIIA is a 70 kDa glycoprotein that consists of a 116 amino acid (aa) extracellular domain (ECD), a 26 aa transmembrane segment, and a 352 aa cytoplasmic region that includes the kinase domain and a PDZbinding motif. Within the ECD, human ActRIIA shares 98% aa sequence identity with mouse and rat ActRIIA. Signaling through ActRIIA is modulated by its interaction with RGMB/ DRAGON, Cripto, Endoglin/CD105, TGFβ RIII/Betaglycan, or BAMBI. These interactions can enhance ligandinduced signaling or interfere with signaling by preventing ActRIIA association with type I receptors. Activininduced responses can also be limited by the enhanced internalization of ActRIIA following its association with the cytoplasmic proteins ARIP1 and ARIP2.