Latent transforming growth factor-beta: structural features and mechanisms of activation

Kidney Int. 1997 May;51(5):1376-82. doi: 10.1038/ki.1997.188.


Transforming growth factor-beta are cytokines with a wide range of biological effects. They play a pathologic role in inflammatory and fibrosing diseases such as nephrosclerosis. TGF-beta s are secreted in a latent form due to noncovalent association with latency associated peptide (LAP), which is a homodimer formed from the propeptide region of TGF-beta. LAP is disulfide linked to another protein, latent TGF-beta binding protein (LTBP). LTBP has features in common with extracellular matrix proteins, and targets latent TGF-beta to the matrix. Activation of latent TGF-beta can be accomplished in vitro by denaturing treatments, plasmin digestion, ionizing radiation and interaction with thrombospondin. The mechanisms by which latent TGF-beta is activated physiologically are not well understood. Results to date suggest an important role for proteases, particularly plasmin, although other mechanisms probably exist. A general model of activation is proposed in which latent TGF-beta is released from the extracellular matrix by proteases, localized to cell surfaces, and activated by cell-associated plasmin.

Publication types

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

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Endothelium, Vascular / physiology
  • Fibrinolysin / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Latent TGF-beta Binding Proteins
  • Transforming Growth Factor beta / chemistry
  • Transforming Growth Factor beta / physiology*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Latent TGF-beta Binding Proteins
  • Transforming Growth Factor beta
  • Fibrinolysin