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The role of proteases in transforming growth factor-beta activation

Gisli Jenkins1

  • 1University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Nottingham NG5 1PB, UK. gisli.jenkins@nottingham.ac.uk

The International Journal of Biochemistry & Cell Biology
|February 5, 2008
PubMed

Insights

Transforming growth factor-beta (TGFbeta) activation is a key checkpoint in biological processes. Proteases like serine and metalloproteinases play distinct roles in releasing active TGFbeta, with integrins being crucial in vivo.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Transforming growth factor-beta (TGFbeta) is vital in development and disease.
  • TGFbeta isoforms (1-3) are latent in extracellular matrix complexes.
  • TGFbeta bioavailability is controlled by activation of these latent complexes.

Purpose of the Study:

  • To review protease-driven TGFbeta activation mechanisms.
  • To discuss the physiological and pathological relevance of TGFbeta activation.
  • To highlight the distinct roles of serine and metalloproteinases in TGFbeta activation.

Main Methods:

  • Review of existing literature on TGFbeta activation pathways.
  • Analysis of protease mechanisms (serine and metalloproteinases) in TGFbeta activation.
  • Comparison of in vitro and in vivo activation mechanisms.

Main Results:

  • Serine proteases (e.g., plasmin) and metalloproteinases (e.g., MMP2) can directly cleave latent TGFbeta.
  • Other proteases (e.g., thrombin, MMP14) utilize integrin-mediated pathways.
  • Integrin-dependent activation is the best-described in vivo mechanism for TGFbeta1, modulated by proteases.

Conclusions:

  • Protease mechanisms for TGFbeta activation differ between enzyme classes.
  • Further in vivo studies are needed to clarify the roles of various proteases.
  • The precise in vivo activation mechanisms for TGFbeta2 and TGFbeta3 require further investigation.

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