Activing/inhibin Subfamily
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Activin /inhibin, as a member of the TGF-β superfamily, is involved in growth and differentiation of many tissues and is crucial for both male and female reproduction by regulating the release of follicle-stimulating hormone (FSH) from the pituitary. There are two activin subfamily members: Activins and Inhibins. They are consisting of two sub-units including sub-unit ßA and sub-unit ßB. Based on the sub-unit, there are three types of activins including Activin A (consisting of ßA ßA), Activin B (consisting of ßB ßB) and Activin AB (consisting of ßA ßB). Activin initiates signaling through two types of transmembrane serine/threonine receptor kinases which are classified into type II (ACVR2A, ACVR2B) and type I (activin like ligands (ALK); ACVR1 (ALK5), ACVR1B (ALK4) and ACVR1C (ALK7)). Upon binding of activin-A to the type II receptor, type I receptor is recruited into the complex and is phosphorylated by type II receptor. Activated type I receptor then phosphorylates Smad proteins. The activated Smads translocate to the nucleus and activate transcription of the target genes.
Activin is regulated by a number of high and low affinity extracellular binding proteins that determine binding to its receptors. The activin/follistatin complex is consisting of two activin molecules and a follistatin molecule, and the complex is crystallized in a dimer form consisting of four activin and two follistatin molecules.
