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The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-beta.
Open accessAbstract
Thrombospondin (TSP) is complexed with transforming growth factor-beta (TGF-beta) in the alpha-granules of stimulated platelets. TSP stripped of associated TGF-beta activity (sTSP) activates latent TGF-beta secreted by bovine aortic endothelial cells (BAE) in culture. To better understand the interactions of TSP with TGF-beta, we investigated which region of sTSP interacts with TGF-beta. The chymotrypsin-resistant core of TSP, which contains the procollagen-like region and the properdin-like type 1 repeats, activated both latent TGF-beta secreted by BAE and a recombinant form of the small latent TGF-beta complex at levels similar to or better than sTSP. The core fragment bound 125I-TGF-beta in solution and shifted the elution profile of 125I-TGF-beta in gel permeation chromatography. Fusion constructs of the type 1, 2, and 3 repeats and the COOH terminus of TSP1 were tested for their ability to activate latent TGF-beta. Only the type 1 construct, containing the three properdin-like repeats of TSP found in the 50-kDa fragment, activated latent TGF-beta. In addition, a polyclonal antibody against the type 1 construct inhibits activation of latent TGF-beta by intact TSP, suggesting that this region is exposed in the intact molecule. These results show that the type 1 properdin-like repeats of TSP are responsible for activating recombinant and endothelial cell-derived latent TGF-beta and that this site is exposed in intact TSP.
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Cited by
Munger, J. S., Huang, X., Kawakatsu, H., Griffiths, M. J. D., Dalton, S. L., Wu, J., Pittet, J.-F., Kaminski, N., Garat, C., Matthay, M. A., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80545-0 · Cited by 2,076
Yu, Q., & Stamenkovic, I. (2000) · Genes & Development · doi:10.1101/gad.14.2.163 · Cited by 1,754
Genetic Analysis of the Mammalian Transforming Growth Factor-β Superfamily
Chang, H., Brown, C. W., & Matzuk, M. M. (2002) · Endocrine Reviews · doi:10.1210/er.2002-0003 · Cited by 787
Activation of latent TGF-β by thrombospondin-1: mechanisms and physiology
Murphy-Ullrich, J. E., & Poczatek, M. (2000) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(99)00029-5 · Cited by 586
Self-citationAngiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects
Battegay, E. J. (1995) · Journal of Molecular Medicine · doi:10.1007/bf00192885 · Cited by 537
Metadata
- Authors
- Schultz-Cherry, S., Lawler, J., & Murphy-Ullrich, J. E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-10
- Volume
- 269
- Issue
- 43
- Pages
- 26783-26788
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1659420318
- Cited by
- 248
- References
- 0
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Schultz-Cherry, S., Lawler, J., & Murphy-Ullrich, J. E. (1994). The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-beta. Journal of Biological Chemistry. https://doi.org/10.1016/s0021-9258(18)47087-1
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