Activin A
exerts its biological activities by binding to the type 2 serine/threonine
kinase Activin RIIA which then noncovalently associates with the type
1 serine/threonine kinase Activin RIB/ALK-4 (7, 11). Signaling through this
receptor complex leads to Smad activation and regulation of activin-responsive
gene transcription (7, 11). The bioactivity of Activin A is regulated
by a variety of mechanisms (11). BAMBI, Betaglycan, and Cripto are cell‑associated
molecules that function as decoy receptors or limit the ability of
Activin A to induce receptor complex assembly (12‑14). The
intracellular formation of Activin A can be prevented by the
incorporation of the beta A subunit into Activin AC or Inhibin A (3, 10).
And the bioavailability of Activin A is restricted by its
incorporation into inactive complexes with alpha 2-Macroglobulin, Follistatin, and
FLRG (15, 16).
Activin A is involved
in the differentiation of various cell and tissue types. The induction of
definitive endoderm by Activin A is required in differentiation protocols of
induced pluripotent stem cells (iPSCs) (17, 18). In vitro models of human
gametogenesis use prolonged Activin A supplementation to human embryonic stem
cells for differentiation into human primordial germ cell-like cells (19).
Activin A can also be used to maintain cells in vitro, as is the case for
iPSC-derived nephron cells that can then be used in disease modeling, drug
screening and in regenerative medicine (20).
Activin
A is an important factor for tumor cells to evade the immune system as Activin
A can act on surrounding immune cells to decrease their antitumor activity
(21). Activin A also promotes migration and growth of tumors, making it a target
for cancer therapies (22). Specifically, research has shown that interfering
with Activin A activity can assist in overcoming CD8 T-cell exclusion and
immunotherapy resistance (23). In bone marrow-derived stem cell transplants for
treatment of diabetes, Activin A enhances migration and homing of stem cells
towards pancreatic lineage (24).
