Recombinant Human Activin AC Heterodimer Protein

Activins and inhibins are TGF-beta superfamily proteins that regulate a wide range of processes including mesoderm induction, reproductive system development and function, liver growth and regeneration, wound healing, and inflammation. Activins and inhibins share a variety of beta subunits, while inhibins also possess a unique alpha subunit. There are four human inhibin beta subunits ( beta_A, beta_B, beta_C, and beta_E) and a single inhibin alpha subunit, each of which adopts a cysteine-knot structure (1 - 5). Activin AC is a 23 kDa heterodimer of beta_A and beta_C subunits (6). Human  beta_A consists of a 20 amino acid (aa) signal sequence, a 290 aa propeptide, and a 116 aa mature segment, while beta_C consists of an 18 aa signal sequence, a 218 aa propeptide, and a 116 aa mature segment (8, 9). The subunit  beta propeptides are required for subunit folding, dimerization, and secretion (10). Mature human beta_A shares 64%, 51%, and 44% aa sequence identity with human beta_B, beta_C, and beta_E, respectively. Sequence identity between human, mouse, and rat is 100% for mature beta_A, and 91% - 93% for mature  beta_C. The beta_A and beta_C subunits are both expressed in the liver, pituitary, ovary, testis, and adrenal gland (1, 6, 11). The beta_C subunit may dimerize with beta_A, beta_B or the inhibin alpha subunit (6, 7). Overexpression of  beta_C results in increased production of Activin AC as well as a reduction in beta_A expression and activin induced signaling (12, 13). The beta_C subunit modulates activin induced effects in a variety of systems by forming intracellular dimers with the beta_A subunit and impeding the release of Activins A, AB, and B (2, 12). Activins signal through heterodimeric receptor complexes composed of type I (Activin RIA or RIB) and type II (Activin RIIA or RIIB) transmembrane Ser/Thr kinases.