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- Title
Latent transforming growth factor-beta: structural features and mechanisms of activation.
- Authors
Munger, J S; Harpel, J G; Gleizes, P E; Mazzieri, R; Nunes, I; Rifkin, D B
- Abstract
Transforming growth factor-beta are cytokines with a wide range of biological effects. They play a pathologic role in inflammatory and fibrosing diseases such as nephrosclerosis. TGF-beta s are secreted in a latent form due to noncovalent association with latency associated peptide (LAP), which is a homodimer formed from the propeptide region of TGF-beta. LAP is disulfide linked to another protein, latent TGF-beta binding protein (LTBP). LTBP has features in common with extracellular matrix proteins, and targets latent TGF-beta to the matrix. Activation of latent TGF-beta can be accomplished in vitro by denaturing treatments, plasmin digestion, ionizing radiation and interaction with thrombospondin. The mechanisms by which latent TGF-beta is activated physiologically are not well understood. Results to date suggest an important role for proteases, particularly plasmin, although other mechanisms probably exist. A general model of activation is proposed in which latent TGF-beta is released from the extracellular matrix by proteases, localized to cell surfaces, and activated by cell-associated plasmin.
- Publication
Kidney international, 1997, Vol 51, Issue 5, p1376
- ISSN
0085-2538
- Publication type
Journal Article
- DOI
10.1038/ki.1997.188