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Unchaining the beast; insights from structural and evolutionary studies on TGFβ secretion, sequestration, and
Ian B Robertson1, Daniel B Rifkin
1Department of Cell Biology, New York University School of Medicine, 550 First Avenue, Cell Biology Floor 6 Room 650, Medical Science Building, New York, NY 10016, United States.
Cytokine & Growth Factor Reviews
|July 16, 2013
Summary
Transforming growth factor beta (TGFβ) requires activation from a latent state. This review explores evolutionary data to understand TGFβ secretion, sequestration, and release mechanisms.
Area of Science:
- Molecular Biology
- Developmental Biology
- Biochemistry
Background:
- Transforming growth factor beta (TGFβ) is crucial for cellular processes but is secreted in an inactive, latent form.
- Activation of latent TGFβ is essential for its signaling and involves various molecular mediators.
- The in vivo roles of many proposed TGFβ activators remain unclear.
Purpose of the Study:
- To review the secretion and activation processes of TGFβ.
- To examine the molecular mechanisms of TGFβ release using evolutionary, sequence conservation, and structural data.
- To differentiate ancient TGFβ activators from more recently evolved ones and establish a potential activation hierarchy.
Main Methods:
- Analysis of evolutionary data.
- Examination of sequence conservation across species.
- Investigation of structural information related to TGFβ and its binding partners.
Main Results:
- Identification of molecular mechanisms governing TGFβ secretion, sequestration, and release.
- Distinction between evolutionarily conserved (ancient) and more recently emerged TGFβ activators.
- Proposal of a hierarchical model for TGFβ activation pathways.
Conclusions:
- Evolutionary and structural analyses provide insights into TGFβ activation mechanisms.
- Understanding the hierarchy of TGFβ activators is key to deciphering its in vivo functions.
- This framework aids in identifying critical mediators of TGFβ mobilization.
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