New insights into the mechanisms of activin action and inhibition

Mol Cell Endocrinol. 2012 Aug 15;359(1-2):2-12. doi: 10.1016/j.mce.2011.06.030. Epub 2011 Jul 8.


Like other members of the transforming growth factor-β (TGF-β) superfamily, activins are synthesised as precursor molecules comprising an N-terminal prodomain and C-terminal mature region. During synthesis, the prodomain interacts non-covalently with mature activin, maintaining the molecule in a conformation competent for dimerisation. Dimeric precursors are cleaved by proprotein convertases and activin is secreted from the cell non-covalently associated with its propeptide. Extracellularly, the propeptide interacts with heparan sulfate proteoglycans to regulate activin localization within tissues. The mature activin dimer exhibits the classic 'open-hand' structure of TGF-β ligands with 'finger-like' domains projecting outward from the cysteine knot core of the molecule. These finger domains form the binding epitopes for type I and II serine/threonine kinase receptors. Activins ability to access its signalling receptors is regulated by the extracellular binding proteins, follistatin, follistatin-like-3, and by inhibins, which, in the presence of betaglycan, sequester type II receptors.

Publication types

  • Review

MeSH terms

  • Activin Receptors, Type I / metabolism
  • Activin Receptors, Type I / physiology
  • Activin Receptors, Type II / chemistry
  • Activin Receptors, Type II / metabolism
  • Activin Receptors, Type II / physiology
  • Activins / chemistry
  • Activins / metabolism
  • Activins / physiology*
  • Amino Acid Motifs
  • Animals
  • Humans
  • Inhibins / metabolism
  • Inhibins / physiology
  • Protein Binding
  • Protein Precursors / metabolism
  • Protein Precursors / physiology*
  • Protein Structure, Tertiary
  • Proteoglycans / metabolism
  • Proteoglycans / physiology
  • Receptors, Transforming Growth Factor beta / metabolism
  • Receptors, Transforming Growth Factor beta / physiology
  • Signal Transduction


  • Protein Precursors
  • Proteoglycans
  • Receptors, Transforming Growth Factor beta
  • Activins
  • betaglycan
  • Inhibins
  • Activin Receptors, Type I
  • Activin Receptors, Type II