Background:

Activin RIB, also known as ALK4, is a glycosylated type I receptor in the superfamily of TGF-β serine/threonine kinase receptors. Activin RIB associates with Activin RIIB to form a receptor complex for activin and inhibin molecules (1). These ligands bind to Activin RIIB which then associates with and phosphorylates the cytoplasmic domain of Activin RIB to initiate signal transduction.Within the ECD, human Activin RIB shares 93% and 95% aa sequence identity with mouse and rat Activin RIB, respectively. It shares 25% - 35% aa sequence identity with other human type I receptors Activin RIA, Activin RIC, BMPR-IA, BMPR-IB, and TGF-β R1. Alternately spliced isoforms of Activin RIB have deletions in the cytoplasmic domain and function as dominant negative inhibitors of activin signaling. Activin receptor signaling is modulated by the direct interaction of Activin RIB with cripto or inhibin binding protein. Activin RIB is excluded from the signaling complex if Activin RIIB first binds inhibin and betaglycan. Activin RIB functions in a wide variety of growth and differentiation processes, including embryonic cell fate and axis determination, cell proliferation and apoptosis, and tumorigenesis.