Activin-B

Activins and inhibins, members of the TGFβ superfamily, are disulfide-linked dimeric proteins that were originally purified from gonadal fluids as proteins that stimulated or inhibited, respectively, pituitary follicle stimulating hormone (FSH) release. These proteins have since been shown to have a wide range of biological activities including: mesoderm induction, neural cell differentiation, bone remodeling, hematopoiesis and reproductive physiology. Activins/inhibins are produced as precursor proteins with an amino-terminal propeptide that is cleaved to release the carboxy terminal bioactive ligands. Activins are homodimers or heterodimers of the various β subunit isoforms, while inhibins are heterodimers of a unique α subunit and one of the various β subunits. Five β subunits (mammalian βA, βB, βC, βE and Xenopus βD) have been cloned. The activin/inhibin nomenclature reflects the subunit composition of the proteins: activin A (βA β A), activin B (βB β B), activin AB (βA β B), inhibin A (αβ A) and inhibin B (αβ B). At present, little is known about the contribution of the other β subunits to activin or inhibin formation and biology. At the amino acid sequence level, the mature human βB subunit is greater than 98% identical to mouse βB, while the human and mouse α subunits share approximately 80% identity. Similarly to other TGFβ family members, activins exert their biological activities through binding to the heterodimeric complex composed of two membrane spanning serinethreonine kinases designated as type I and type II. Two forms of activin receptor type I (Act RI A and Act RIB) and two forms of activin receptor type II (Act RIIA and Act RIIB) have been identified. Activin binds directly to Act RII, the complex then associates with Act RI and initiates signaling. Besides activins, Act RII has been shown to bind certain other TGFβ superfamily members. Inhibin A has been shown to bind with lowaffinity to Act RII. The existence of a distinct inhibinspecific receptor and/or signal transduction pathway has been hypothesized.