Protease inhibitors and proteolytic signalling cascades in insects

Biochimie. 2010 Dec;92(12):1749-59. doi: 10.1016/j.biochi.2010.09.004. Epub 2010 Sep 17.


Proteolytic signalling cascades control a wide range of physiological responses. In order to respond rapidly, protease activity must be maintained at a basal level: the component zymogens must be sequentially activated and actively degraded. At the same time, signalling cascades must respond precisely: high target specificity is required. The insects have a wide range of trapping- and tight-binding protease inhibitors, which can regulate the activity of individual proteases. In addition, the interactions between component proteases of a signalling cascade can be modified by serine protease homologues. The suicide-inhibition mechanism of serpin family inhibitors gives rapid turnover of both protease and inhibitor, but target specificity is inherently broad. Similarly, the TEP/macroglobulins have extremely broad target specificity, which suits them for roles as hormone transport proteins and sensors of pathogenic virulence factors. The tight-binding inhibitors, on the other hand, have a lock-and-key mechanism capable of high target specificity. In addition, proteins containing multiple tight-binding inhibitory domains may act as scaffolds for the assembly of signalling complexes. Proteolytic cascades regulated by combinations of different types of inhibitor could combine the rapidity of suicide-inhibitors with the specificity lock-and-key inhibitors. This would allow precise control of physiological responses and may turn out to be a general rule.

Publication types

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

MeSH terms

  • Animals
  • Insect Proteins / metabolism*
  • Insecta / metabolism*
  • Macroglobulins / metabolism
  • Peptide Hydrolases / metabolism*
  • Protease Inhibitors / classification
  • Protease Inhibitors / metabolism*
  • Serpins / metabolism
  • Signal Transduction*


  • Insect Proteins
  • Macroglobulins
  • Protease Inhibitors
  • Serpins
  • Peptide Hydrolases