Human Activin A protein is a member of the TGFβ superfamily of growth factors involved in stem cell differentiation and maintenance, regulation of embryogenesis, development of the reproductive system, wound healing and regulation of immune responses. Activin A signalling is modulated by the glycoprotein follistatin, production is which is stimulated by Activin A forming a feedback loop (1) , and inhibins.
Follistatin binds to and neutralises members of the TGF-β superfamily, preventing signalling by shielding the type II and I receptor binding sites (2-4).
Activins are disulfide-linked homo- and heterodimers of four inhibin β chains. The best characterized are Activin A and Activin B, homodimers of inhibin βA and inhibin βB respectively. Activins, like all other members in the TGF-β superfamily, are synthesized as larger precursors consisting of an N-terminal signal peptide, a pro-domain of 250–350 residues and a highly conserved mature domain. The pro-domain, which is cleaved off in the mature protein, has important roles in the biosynthesis, stabilization, transportation and signalling of the growth factors (5).
Recombinant Activin A is used for maintenance of pluripotency in many human induced-pluripotent stem cell and human embryonic stem cell lines3, and to induce stem cell differentiation into endoderm(6) and other cell fates.
Follistatin resistant activin A (FRACTA) has been developed in the lab of Marko Hyvönen at the University of Cambridge. FRACTA has been engineered to be unimpeded by follistatin while maintaining its ability to bind type I and II receptors.