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The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-beta.

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Schultz-Cherry, S, Lawler, J, Murphy-Ullrich, J E·1994·Journal of Biological Chemistry

Abstract

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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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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CoChat. (2026). Citation check: The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-beta. https://app.cochat.ai/papers/10.1016/s0021-9258(18)47087-1
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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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