title: New insights into the mechanisms of activin action and inhibition.
abstract: 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.
authors.affiliation: Prince Henry's Institute of Medical Research, 246 Clayton Road, Clayton, Vic 3168, Australia.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Walton
authors.forename: Yogeshwar
authors.initials: Y
authors.lastname: Makanji
authors.forename: Craig A
authors.initials: CA
authors.lastname: Harrison
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism / Q000502:physiology; D030301:Activin Receptors, Type II / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D028341:Activins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D020816:Amino Acid Motifs; D000818:Animals; D006801:Humans; D007265:Inhibins / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000378:metabolism / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction
chemical_list: D011498:Protein Precursors; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D028341:Activins; C071736:betaglycan; D007265:Inhibins; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II