Bioavailability of TGF-Beta in Breast Cancer
Abstract
The Transforming Growth Factor beta (TGF-Beta) superfamily includes three isoforms designated TGF-Beta1, Beta2, Beta3. All three isoforms are secreted as latent complex where the TGF-Beta 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-Beta bioavailability. Proposed activation mechanisms include proteolysis and conformational changes. Previous work from our laboratory showed that latent TGF-Beta1 (LTGF-Beta1) is efficiently activated upon exposure to reactive oxygen species (ROS). ROS activation is restricted to the LTGF-Beta1 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2005
- Accession Number
- ADA444006
Entities
People
- Joni Mott
- Mary H. Barcellos-hoff
- Michael Jobling
Organizations
- University of California, Berkeley