Protease inhibitors and proteolytic signalling cascades in insects.
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.
Gubb
David
D
Department of Functional Genomics, CICbioGUNE Institute, Bizkaia Technology Park, Ed. 801A, 48160 Derio, Spain. dgubb@cicbiogune.es
Sanz-Parra
Arantza
A
Barcena
Laura
L
Troxler
Laurent
L
Fullaondo
Ane
A
D000818:Animals; D019476:Insect Proteins / Q000378:metabolism*; D007313:Insecta / Q000378:metabolism*; D008259:Macroglobulins / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000145:classification / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism; D015398:Signal Transduction
D019476:Insect Proteins; D008259:Macroglobulins; D011480:Protease Inhibitors; D015843:Serpins; D010447:Peptide Hydrolases