Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology

Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):59-69. doi: 10.1016/s1359-6101(99)00029-5.


Regulation of the activation of latent TGF-beta is essential for health as too much or too little TGF-beta activity can have serious, deleterious consequences. The processes that control conversion of the precursor to the biologically active form of TGF-beta in vivo are not well characterized. We have identified a mechanism for the activation of latent TGF-beta that involves binding of the secreted and extracellular matrix protein, thrombospondin-1 (TSP-1), to the latent precursor. Specific sequences in TSP-1 and in the precursor portion (the latency associate peptide-LAP) have been determined to be essential for activation of latent TGF-beta by TSP-1. It is thought that binding of TSP-1 to the latent complex induces a conformational rearrangement of the LAP in such a manner as to prevent the LAP from conferring latency on the mature domain of TGF-beta. A TSP-dependent mechanism of activation may be locally important during wound healing and in post-natal development of epithelial structures. The possible involvement of TSP-1 in TGF-beta activation during several disease processes is also discussed.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / ultrastructure
  • Glomerulonephritis, Membranoproliferative / metabolism*
  • Humans
  • Peptide Fragments*
  • Protein Precursors*
  • Proteins / metabolism
  • Pulmonary Fibrosis / metabolism*
  • Rats
  • Tamoxifen / pharmacology
  • Thrombospondin 1 / metabolism*
  • Thrombospondin 1 / physiology
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / physiology
  • Transforming Growth Factor beta1
  • Wound Healing*


  • Peptide Fragments
  • Protein Precursors
  • Proteins
  • Thrombospondin 1
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tamoxifen