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Latent transforming growth factor-β: Structural features and mechanisms of activation
Open accessAbstract
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.
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Sato, Y., Tsuboi, R., Lyons, R., Moses, H., & Rifkin, D. B. (1990) · The Journal of cell biology · doi:10.1083/jcb.111.2.757 · Cited by 444
Self-citationOsteoclast synthesis and secretion and activation of latent transforming growth factor β
Oursler, M. J. (1994) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650090402 · Cited by 153
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Derynck, R., Akhurst, R. J., & Balmain, A. (2001) · Nature Genetics · doi:10.1038/ng1001-117 · Cited by 2,275
Yu, Q., & Stamenkovic, I. (2000) · Genes & Development · doi:10.1101/gad.14.2.163 · Cited by 1,754
Lee, C. G., Homer, R. J., Zhu, Z., Lanone, S., Wang, X., Koteliansky, V., Shipley, J. M., Gotwals, P., Noble, P., Chen, Q., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.809 · Cited by 940
TGF-β signaling in health and disease
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Metadata
- Authors
- Munger, J. S., Harpel, J. G., Gleizes, P.-E., Mazzieri, R., Nunes, I., & Rifkin, D. B.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 1997-05
- Volume
- 51
- Issue
- 5
- Pages
- 1376-1382
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W1966908061
- Cited by
- 511
- References
- 2
- FWCI
- 11.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Munger, J. S., Harpel, J. G., Gleizes, P.-E., Mazzieri, R., Nunes, I., & Rifkin, D. B. (1997). Latent transforming growth factor-β: Structural features and mechanisms of activation. Kidney International. https://doi.org/10.1038/ki.1997.188
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