Beta A versus beta B: is it merely a matter of expression?

Abstract

Activins are members of the transforming growth factor (TGF) beta (β) superfamily of proteins that function in a wide array of physiological processes. Like other TGFβ ligands, activins are biologically active as dimers. An activin molecule is comprised of two β-subunits, of which four isoforms have been identified: βA, βB, βC, and βE. The most widely studied activins to date are activin A (βA/βA), activin B (βB/βB), and activin AB (βA/βB). Inhibin is a naturally occurring activin antagonist that consists of an α-subunit disulfide-linked to one of the activin β-subunits, producing inhibin A (α/βA), or inhibin B (α/βB). The development of assays distinguishing between different forms of activins and inhibins, along with knock-in and knock-out models, have provided evidence that the βA- and βB-subunits have independent and separate roles physiologically. Additionally, evaluation of ligand–receptor interactions indicates significant differences in receptor affinity between activin isoforms, as well as between inhibin isoforms. In this review we explore the differences between activin/inhibin βA- and βB-subunits, including expression patterns, binding properties, and the specific structural aspects of each. From the growing pool of knowledge regarding activins and inhibins, the emerging data support the hypothesis that βA- and βB-subunits are functionally differently.