Transforming growth factor-β complexes with thrombospondin

Joanne E. Murphy-Ullrich, Stacey Schultz-Cherry, Magnus Höök

Research output: Contribution to journalArticle

213 Scopus citations

Abstract

Thrombospondin (TSP) was demonstrated to inhibit the growth of bovine aortic endothelial cells, an activity that was not neutralized by antibodies to TSP or by other agents that block TSP-cell interactions but that partially was reversed by a neutralizing antibody to transforming growth factor-β (TGF-β). Similar to TGF-β, TSP supported the growth of NRK-49F colonies in soft agar in a dose-dependent manner, which required epidermal growth factor and was neutralized by anti-TGF-β antibody. Chromatography of a TSP preparation did not separate the TGF-β-like NRK colony-forming activity from high molecular weight protein. However, when chromatography was performed at pH 11, this activity was dissociated from TSP. These results suggest that at least some growth modulating activities of TSP are due to TGF-β associated with TSP by strong non-covalent forces. Most of the active TGF-β released from platelets after degranulation was associated with TSP/ as demonstrated by anti-TSP immunoaffinity and gel permeation chromatography. 125I-TGF-β binds to purified TSP in an interaction that is specific in the sense that bound TGF-β could be displaced by TGF-depleted TSP but not significantly by native TSP, heparin, decorin, alpha2-macroglobulin, fibronectin, or albumin. Hence, TGF-β can bind to TSP, and the complex forms under physiological conditions. Furthermore, TSP-associated TGF-0 is biologically active, and the binding of TGF-/3 to TSP may protect TGF-/3 from extracellular inactivators.

Original languageEnglish (US)
Pages (from-to)181-188
Number of pages8
JournalMolecular Biology of the Cell
Volume3
Issue number2
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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