Activin receptors

Activin receptors are structurally related membrane proteins that belong to the transforming growth factor (TGF)-β receptor superfamily. Two main types, I and II activin receptors have been identified which consist of an extracellular ligand-binding domain, a transmembrane domain, and an intracellular domain containing a serine/threonine kinase region. A dimer of each of these receptors participates in forming a receptor complex on the cell surface with the dimeric ligand. This activated complex signals intracellularly through the kinase domain of type I receptors to recruit and activate the intracellular transducers of activin: receptor-regulated (R)-Smad proteins. The latter form a hetero-oligomeric complex with a common (Co)-Smad protein shared by all TGF-β-induced signaling pathways. This complex then translocates to the nucleus and forms a transcription complex that binds to promoters and regulates the expression of several genes. One of these genes encodes an inhibitory (I)-Smad protein which negatively regulates further signaling. Activin receptors are widely expressed in various organs and cell types. Activin binding to its receptors leads to a plethora of biological functions which are antagonized by inhibin that competes with activin for binding to the receptor. In addition, activin receptors bind additional ligands and thus mediate functions which are not necessarily related to activin. Studies of mutant activin receptors in different species, including mammals, revealed dramatic phenotypes that demonstrate the crucial role of these receptors in early mesoderm induction. Accordingly, activin receptors control the expression of several mesoderm differentiation genes. Furthermore, activin receptors control embryonic axis symmetry determination and organ development and are also involved in the control of specific adult organ function.