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 signal through heterodimeric receptor complexes composed of type I (Activin RIA or RIB) and type II (Activin RIIA or RIIB) transmembrane Ser/Thr kinases. 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 (1‑3). Activins are disulfide‑linked homodimers or heterodimers of beta subunits, while Inhibins contain the alpha subunit and beta A
or beta B
. Human beta C
consists of an 18 aa signal sequence, a 218 aa propeptide, and a 116 aa mature segment (4). Mature human beta C
shares 51%, 53%, and 64% aa sequence identity with human beta A
, beta B
, and beta E
, respectively. It shares 93% and 91% aa sequence identity with mouse and rat beta C
, respectively. The expression of beta C
is restricted compared to the widespread distribution of beta A
and beta B
. Activin C is expressed as an approximately 20 kDa dimer predominantly by hepatocytes but also by multiple cell types in the male and female reproductive tracts, posterior pituitary and adrenal glands, and nociceptive afferent dorsal root ganglia neurons (5‑7). The beta C
subunit regulates Activin induced effects in a variety of systems by forming intracellular dimers with the beta A
subunit and impeding the release of Activins A and AB (8, 9). It also functions extracellularly by interfering with Activin A‑receptor interactions (6, 7, 10). beta C
can additionally form heterodimers with the beta B
or beta E
subunits (9, 11, 12).
- Butler, C.M. et al. (2005) Cytokine Growth Factor Rev. 16:377.
- Werner, S. and C. Alzheimer (2006) Cytokine Growth Factor Rev. 17:157.
- Walton, K.L. et al. (2012) Mol. Cell. Endocrinol. 359:2.
- Hötten, G. et al. (1995) Biochem. Biophys. Res. Commun. 206:608.
- Gold, E.J. et al. (2004) Mol. Cell. Endocrinol. 222:61.
- Wada, W. et al. (2004) Am. J. Physiol. Endocrinol. Metab. 287:E247.
- Liu, X.-J. et al. (2012) Brain 135:391.
- Mellor, S.L. et al. (2003) Endocrinology 144:4410.
- Mellor S.L. et al. (2000) J. Clin. Endocrinol. Metab. 85:4851.
- Gold, E. et al. (2009) Am. J. Pathol. 174:184.
- Vejda, S. et al. (2002) J. Mol. Endocrinol. 28:137.
- Wada, W. et al. (2005) Endocr. J. 52:169.