New insights into the mechanisms of activin action and inhibition
- 作者：Kelly L. Walton ; Yogeshwar Makanji ; Craig A. Harrison ; Craig.Harrison@princehenrys.org
- 关键词：Activin ; Inhibin ; Transforming growth factor-尾 ; Follistatin ; Betaglycan ; Prodomain
- 刊名：Molecular and Cellular Endocrinology
- 出版年：2012
- 期刊代码：109_03037207
- 类别：bio
- 出版时间：15 August, 2012
- 卷：359
- 期：1-2
- 页码：2-12
- 文件大小：1222 K
摘要
Like other members of the transforming growth factor-尾 (TGF-尾) 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 鈥榦pen-hand鈥?structure of TGF-尾 ligands with 鈥榝inger-like鈥?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.