Protein Kallikrein

Sustarsic, D.L., McPartland, R.P. and Rapp, J.P. (1981). Developmental patterns of blood pressure and urinary protein, kallikrein, and prostaglandin E2 in Dahl salt-hypertension susceptible rats. ]. Lab. Clin. Med., 98, 599-606... 

An alternative pathway for activating the cascade has recently been demonstrated in which factor XII is absent from the reaction mixture [42-45]. Two different groups have isolated two different proteins, each of which seems to activate the HK-prekallikrein complex. One is heat-shock protein 90 [46] and the other is a prolylcarboxypeptidase [47]. Neither protein is a direct prekallikrein activator as is factor Xlla or factor Xllf because each activator requires HK to be complexed to the prekallikrein. In addition, the reaction is stoichiometric, thus the amount of prekallikrein converted to kallikrein equals the molar input of heat-shock protein 90 (or prolylcarboxypeptidase). These proteins can be shown to contribute to factor Xll-independent prekallikrein activation and antisera to each protein have been shown to inhibit the process. When whole endothelial cells are incubated with normal plasma or factor Xll-deficient plasma, the rate of activation of the deficient plasma is very much slower than that of the normal plasma, the latter being factor Xll-dependent [45]. Under normal circumstances (with factor XII present), formation of any kallikrein will lead to factor Xlla formation even if the process were initiated by one of these cell-derived factors. 

Cl-Inh belongs to a superfamily of serine protease inhibitors (serpins) and is a major inhibitor of F-XIIa and kallikrein. It is also an inhibitor of activated complement factors C1 q, C1 r, and C1 s. C1 -Inh thus regulates the activation of two important plasma cascade systems. Proteases induce a conformational change in the plasma protein a2-M, which results in entrapment of the protease into the a2-M cage (B4). In vivo, a2-M acts as a second inhibitor of kallikrein. 

Bacterial products such as lipopolysaccharides (endotoxins) and cytokines (IL-2) are able to activate the contact system in vitro and in vivo (D9, H4, H7, M41). Immediately after severe trauma or after surgical intervention and particularly during sepsis, a reduction of plasma contact system proteins has been found (C10, K1, N9). Gel filtration studies of plasma demonstrated that plasma PK after activation becomes complexed with a2-M and Cl-Inh (W4). These complexes are rapidly eliminated from the circulation in vivo. In experimental studies in which pulmonary insufficiency was induced in dogs, a significant reduction of plasma kallikrein inhibitors was observed together with reduced HMK. Analysis of the relation be-... 

Additional protein constituents of the intrinsic cascade include prekallikrein, an 88 kDa protein zymogen of the protease kallikrein, and high molecular mass kininogen, a 150 kDa plasma glycoprotein that serves as an accessory factor. 

Tincture of the dried seed, on agar plate at a concentration of 30 p,L/disc, was inactive on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Extract of 10 g plant material in 100 mL ethanol was used b Anticoagulation activity. Serpin BSZx (an inhibitor of trypsin and chemotrypsin) inhibited thrombin, plasma kallikrein, factor Vlla/tissue factor, and factor Xa at heparin-independent association rates. Only factor Xa turned a significant fraction of BSZx over as substrate. Activated protein C and leukocyte elastase were slowly inhibited by BSZx, whereas factor Xlla, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein, and elastase were not or only weakly affected. Trypsin from Fusarium was not inhibited, while interaction with subtilisin Carlsberg and Novo was rapid, but most BSZx was cleaved as a substrate L... 

Elastases—1, 2, 3A, 3B (protease E), medullasin Hepatocyte growth factor activator Glandular kallikreins—EGF-binding protein A-C, NGF-y, renin-y, prostate-specific antigen (PSA), and tonin Mite fecal allergen Der pill... 

Kinins are potent vasodilator peptides formed enzymatically by the action of enzymes known as kallikreins or kininogenases acting on protein substrates called kininogens. The kallikrein-kinin system has several features in common with the renin-angiotensin system. 

Aprotinin is a polypeptide consisting of 58 amino acid residues derived from bovine lung tissues and shows inhibitory activity toward various proteolytic enzymes including chymo-trypsin, kallikrein, plasmin, and trypsin. It was also one of the first enzyme inhibitors used as an auxiliary agent for oral (poly)peptide administration. The co-administration of aprotinin led to an increased bioavailability of peptide and protein drugs [5,44,45], The Bowman-Birk inhibitor (71 amino acids, 8 kDa) and the Kunitz trypsin inhibitor (184 amino acids, 21 kDa) belong to the soybean trypsin inhibitors. Both are known to inhibit trypsin, chymotrypsin, and elastase, whereas carboxypeptidase A and B cannot be inhibited [7,46],... 

Structural Features of the Human Tissue Kallikrein Genes and Proteins. 20... 

Kallikreins are found in both primates and nonprimates. Kallikrein genes and proteins have been identified in six different mammalian orders Primates, Rodentia, Carnivora, Proboscidea, Perissodactyla, and Artiodac-tyla [4]. The number of kallikreins varies among species, and kallikreins in rodents and other animal species have been extensively described in a number of excellent reviews [2, 5-8]. In this section, we provide only a quick overview and some recent updates about kallikrein families in different species, with special emphasis on their structural and localization relationships with the... 

Official and Other Gene and Protein Names for Members of the Human Kallikrein Gene Family ... 

Summary of Human Tissue Kallikrein Protein Characteristics... 

The crystal structure has been revealed for some rodent kallikreins. The three-dimensional structure of a horse orthologue of the human hK3 has also been reported [28]. In contrast, hKl and hK6 are the only human kallikreins for which crystal structures have been determined [48-50]. Most of the discussion in this section is derived from comparative model building of the human kallikrein proteins. 

Kallikreins can be roughly divided into two categories, the classical kallikreins (hKl, hK2, and hK3) and the new kallikreins. The new kallikreins appear to be unique in their three-dimensional structure and share some features with trypsins and other features with the classical kallikreins. Comparative protein models show that the pattern of hydrophobic side-chain packing in the protein core is nearly identical in all human kallikreins, and the observed differences occur within the solvent-exposed loop segments. 

From a structural point of view, kallikreins belong to the serine protease family of enzymes. The essential features of serine proteases that are preserved in the kallikreins can be summarized as follows only one serine residue of the protein is catalytically active two residues, a histidine and an... 

Another possible mechanism for kallikrein action in physiology and pathobiology is the activation of proteinase-activated receptors (PARs). PAR is a recently described family of G-protein-coupled receptors with seven transmembrane domains that are stimulated by cleavage of their N-termini by a serine protease rather than by ligand-receptor interaction [184-186]. Four PARs have been identified so far, of which PARI, PAR3,... 

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