Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A critical step in the influenza virus replication cycle is the cleavage activation of the HA precursor. Cleavage activation of influenza HA enables fusion with the host endosome, allowing for release of the viral genome into the host cell. To date, studies have determined that HA activation is driven by trypsin-like host cell proteases, as well as yet to be identified bacterial proteases. Although the number of host proteases that can activate HA is growing, there is still uncertainty regarding which secreted proteases are able to support multicycle replication of influenza. In this study, we have determined that the kallikrein-related peptidases 5 and 12 are secreted from the human respiratory tract and have the ability to cleave and activate HA from the H1, H2, and H3 subtypes. Each peptidase appears to have a preference for particular influenza subtypes, with kallikrein 5 cleaving the H1 and H3 subtypes most efficiently and kallikrein 12 cleaving the H1 and H2 subtypes most efficiently. Cleavage analysis using HA cleavage site peptide mimics revealed that the amino acids neighboring the arginine cleavage site affect cleavage efficiency. Additionally, the thrombolytic zymogens plasminogen, urokinase, and plasma kallikrein have all been shown to cleave and activate influenza but are found circulating mainly as inactive precursors. Kallikrein 5 and kallikrein 12 were examined for their ability to activate the thrombolytic zymogens, and both resulted in activation of each zymogen, with kallikrein 12 being a more potent activator. Activation of the thrombolytic zymogens may therefore allow for both direct and indirect activation of the HA of human-adapted influenza viruses by kallikrein 5 and kallikrein 12.
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PMID:Cleavage activation of human-adapted influenza virus subtypes by kallikrein-related peptidases 5 and 12. 2361 74

Little is known about the role of the kallikrein-kinin system in chronic spontaneous urticaria (CSU). Kallikrein 5 (KLK5), a trypsin-like enzyme, is the most abundant in the skin and plays a role in itching and inflammatory reaction. In this study, we determined plasma KLK5 concentration, and its associations with acute phase response in CSU patients. Concentrations of KLK5 in plasma and CRP in serum were measured in patients with CSU of varying severity and in the healthy subjects. Plasma KLK5 concentrations were significantly lower in CSU (all) and moderate-severe CSU patients, as compared with the controls. There were no significant differences in KLK5 concentration in mild CSU patients as compared with the healthy subjects and moderate-severe CSU patients. No correlation was observed between KLK5 and CRP concentrations in the patients. It may be considered that circulating kallikrein 5 is down-regulated in CSU patients, however its potential role and the possible underlying mechanism are unknown.
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PMID:Decreased plasma kallikrein 5 concentrations in patients with chronic spontaneous urticaria. 2868 45