Bioavailability of TGF-Beta in Breast Cancer
Abstract
The Transforming Growth Factor beta (TGF-b) superfamily includes three isofroms designated TGF-b1, b2 and b3. All three isoforms are secreted as latent complex where the TGF-b cytokine is non-covalently associated with an isoform specific latency-associated peptide (LAP). Mature cytokine binds cell surface receptors only after release from its LAP making extracellular activation a critical regulatory point for TGF-b bioavailability. Proposed activation mechanisms include proteolysis and conformational changes. Previous work from our laboratory showed that latent TGF-b1 (LTGF-b1) is efficiently activated upon exposure to reactive oxygen species (ROS). ROS activation is restricted to the LTGF-b1 isoform. Because of the amino acid sequence differences between the three LAPs, we postulate that the specificity of this activation mechanism lies within the LAP. Furthermore, we hypothesize that the presence of a metal in the latent complex could provide a redox active center for this process. Redox mediated activation provides a novel mechanism for TGF-b participation in tissues undergoing oxidative stress. Moreover, this would allow TGF-b1 to act both as a sensor of oxidative stress within tissues as well as a transducer of that signal by binding to its cellular receptors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA463510
Entities
People
- Irineu Illa-bochaca
- Mary H. Barcellos-hoff
Organizations
- University of California, Berkeley