Proteolytic cascade

A proteolytic cascade occurs when one peptidase activates the next in a proteolytic pathway, and this in turn activates the next and so on. This is a mechanism to amplify the initial signal, because one peptidase molecule can activate many zymogen molecules. Examples of proteolytic cascades include blood coagulation, activation of digestive peptidases in the intestine, and apoptosis. 

The early components of the complement pathway, including Cl, are proteases that activate their substrate by limited cleavage. Activated Cl now activates several molecules of the next component by proteolysis, each of which activates several molecules of the next component by proteolysis, and so on. Therefore, the early steps in complement activation consist of a proteolytic cascade in which more and more molecules are activated at each step. Component C3 is the key component whose cleavage leads to the assembly of... 

The activation of enzyme precursors is likely to be of central importance. A significant fraction of the total SCCE present in the stratum corneum is in the form of inactive proenzyme.53,54 A change in the ratio of precursor to active enzyme may be expected to cause marked changes in the rate of corneodesmosomal degradation. In vitro pro-SCCE can be activated by pancreatic trypsin.39 As mentioned earlier SCTE has been suggested to act as an SCCE activator, but this remains to be elucidated. It is possible that SCCE is just one of a number of enzymes constituting a proteolytic cascade in the stratum corneum, in which one enzyme serves as activator of another enzyme. 

Rosenberg GA,Navratil M, Barone F, Feuerstein G (1996) Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Flow Metab 16 360-366... 

Nakatani, T., Kim, H. J., Kaburagi, Y., Yasuda, K., and Ezaki, O. 2002. A low fish oil inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases SREBP-1 mRNA in mice liver relationship to anti-obesity. J. Lipid Res., 44, 369-379. 

As with all complex biological systems we should not forget the close interplay between oxidative and proteolytic systems (see Fig. 2). For example, it has been shown that at a localised inflammatory site, oxidative inactivation of protease inhibitors may lead to a proteolytic cascade resulting in down-stream MMP activation through the localised action of serine proteinases activating previously latent MMPs (see Fig. 2). Equally, the generation of active MMPs (post-oxidant exposure) may be involved in the site-specific catalytic inactivation of serine-protease inhibitors [59] at an inflammatory site with the consequent generation of an elevated serine protease load and connective tissue proteolysis (see Fig. 2). 

Rosenberg GA, NavratU M, Barone F, Feuerstein G (1996a) Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Flow Metab 16 360-366 Rosenberg GA, Scremin O, Estrada E, Kyner WT (1992) Arginine vasopressin Vl-tmtagonist and atrial natriuretic peptide reduce hemorrhagic brtiin edema in rats. Stroke 23 1767-1774... 

Shaham S. 1998. Identification of multiple Caenorhabditis elegans caspases and their potential roles in proteolytic cascades. J. Biol Chem. 273 35109-17... 

In addition to the direct effects which sulphur mustard may have in initiating proteolytic cascades, other sources of proteolytic enzymes have to be considered, the most important of these being the various inflammatory cell types that have been described as part of the sulphur mustard-induced cutaneous injury in various species (Papirmeister et al, 1984 Vogt et al., 1984 Mitcheltree et al, 1989 Mershon et al., 1990). 

A FIGURE 15-17 Dorsoventral axis determination in Drosophila. This process relies on two signal systems, one in follicle cells and the other in the oocyte or embryo or both, plus a proteolytic cascade within the perivitelline space. 

A blood clot is formed mainly from a network of crosslinked fibrin molecules that traps platelets, erythrocytes, and other materials to form a solid clot. The aggregation and cross-linking of fibrin is the final stage of a proteolytic cascade or pathway which is triggered by one or both of two mechanisms the intrinsic pathway and the extrinsic pathway. 

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