TGF-beta: from latent to active

Microbes Infect. 1999 Dec;1(15):1255-63. doi: 10.1016/s1286-4579(99)00259-2.


The transforming growth factor-betas (TGF-betas) are synthesized as precursor proteins that are modified intracellularly prior to secretion. One of the most relevant intracellular modifications is the cleavage of the C-terminal pro-region from the N-terminal portion of the protein. The C-terminal pro-region is referred to as the latency-associated peptide (LAP) while the N-terminal region is called the mature TGF-beta or active TGF-beta. However, with some exceptions the LAP noncovalently associates with the mature TGF-beta prior to secretion. When the mature TGF-beta is associated with the LAP it is called L-TGF-beta and cannot interact with its receptor and has no biological effect. The TGF-betas and their receptors are very ubiquitously expressed, suggesting that the regulation of TGF-beta activity is likely to be complex and multifactorial. However, one of the most important means of controlling the biological effects of TGF-beta is the regulation of converting L-TGF-beta to active TGF-beta. The current literature supports two major mechanisms of activation of L-TGF-beta and suggests that the mechanism of activation of L-TGF-beta may be varied and context-dependent. For TGF-beta to become biologically active the LAP has to be either released from its associations with L-TGF-beta or undergo conformational change such that the LAP is not released from the L-TGF-beta complex but exposes the TGF-beta receptor binding site. Since TGF-beta has been associated with the pathogenesis of numerous diseases, the various mechanisms of activation of L-TGF-beta in context offer the possibility of controlling TGF-beta activity localized to the organ of involvement and to a more specific disease process.

Publication types

  • Review

MeSH terms

  • Gene Expression Regulation*
  • Humans
  • Peptide Fragments*
  • Protein Precursors*
  • Proteins / metabolism*
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1


  • Peptide Fragments
  • Protein Precursors
  • Proteins
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1