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

J Biol Chem. 1994 Oct 28;269(43):26783-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aorta / cytology
  • Cattle
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Adhesion Molecules / pharmacology
  • Chromatography, Gel
  • Chymotrypsin / metabolism
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / metabolism*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / pharmacology
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Procollagen / chemistry
  • Properdin / chemistry
  • Protein Binding
  • Protein Conformation
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Repetitive Sequences, Nucleic Acid
  • Structure-Activity Relationship
  • Thrombospondins
  • Transforming Growth Factor beta / metabolism*


  • Cell Adhesion Molecules
  • Membrane Glycoproteins
  • Peptide Fragments
  • Procollagen
  • Recombinant Fusion Proteins
  • Thrombospondins
  • Transforming Growth Factor beta
  • Properdin
  • Chymotrypsin