Expression and Processing of the Activin-A/Erythroid Differentiation Factor Precursor: A Member of the Transforming Growth Factor-β Superfamily

Abstract

The biosynthesis and intracellular processing of the polypeptide precursor of the beta A-chain of the fertility hormone inhibin were assessed by infecting a wide spectrum of cell types with a recombinant vaccinia virus. Most cell lines, including follicular granulosa cells, secrete both prohormone and mature hormone as homodimers (activin) composed of disulfide-linked subunits of 54 kDa (proactivin-A) and 14 kDa (activin-A), respectively, and a small amount of prohormone-mature hormone heterodimers. Mature activin is secreted from mouse pituitary cells (AtT-20), while pig kidney cells [PK(15)] secrete mostly proactivin. More prohormone is secreted in the presence of NH4Cl, suggesting that prohormone processing is facilitated by low pH. Proactivin-A is not a ligand for the mannose-6-phosphate/insulin growth factor-II receptor. The recombinant activin stimulates FSH release from pituitary cells and differentiates erythroleukemia cell lines in vitro.