Evolution of Kallikreins

Cross-Talk Between Kallikreins A Possible Novel Enzymatic Cascade Pathway 

Interactions between serine proteases are common, and substrates of serine proteases are usually other serine proteases that are activated from an inactive precursor [66]. The involvement of serine proteases in cascade pathways is well documented. One important example is the blood coagulation cascade. Blood clots are formed by a series of zymogen activations. In this enzymatic cascade, the activated form of one factor catalyzes the activation of the next factor. Very small amounts of the initial factors are sufficient to trigger the cascade because of the catalytic nature of the process. These numerous steps yield a large amplification, thus ensuring a rapid and amplified response to trauma. A similar mechanism is involved in the dissolution of blood clots. A third important example of the coordinated action of serine proteases is the intestinal digestive enzymes. The apoptosis pathway is another important example of coordinated action of other types of proteases. 

Recent experiments have shown that hK3 can be activated by hK15 [161]. hK4 has also recently been shown to activate hK3 and does so much more efficiently compared to hK2 [106]. hK5 is predicted to be able to activate hK7 in the skin [103]. The activation of hK3 by hK2 is also possible. Although Takayama et al., reported the ability of hK2 to activate hK3 [162], Denmeade et al. reported the opposite [105] and hypothesized that additional proteases may be required. It will be interesting to study all possible combinations of interactions among kallikreins, especially those 

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