Cascade activation

Table 1. Physiochemical properties of proteins of the contact activation cascade... 

Tokumitsu, H. and Soderling, T. R., 1996, Requirements for calcium and calmodulin in the calmodulin kinase activation cascade, J Biol Chem, 271, pp 5617-22. 

Oxidatively generated oxocarbenium ions have been used for intramolecular epoxide activation. Cascade reactions to form oligotetrahydrofuran products that demonstrated a strong preference for the exo-cyclization pathway were achieved in good yields when disubstituted epoxides were used as substrates. High stereoselectivity was observed in these reactions, with complementary diastereomers being formed from diastereomeric (g) epoxides.257... 

Engineered IgG antibodies have been constructed with altered affinity to human Fey receptors and altered potency in vitro and in animal models [14, 31-33]. Mutations of critical residues in the Fc region (CH2 domain or the hinge region joining CH1 and CH2) have enhanced or decreased antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) [33-37]. In addition, alterations in residues located at the CH2 domain of I gC, i involved in binding with Clq protein, a component of the complement activation cascade, resulted in a significant increase in CDC activity [34, 35]. 

Platelet activation cascade in response to different agonists and the site of action of different antiplatelet agents. 

A series of proteins collectively called the complement participate in the immune response to the entry of foreign cellular or viral material into the organism. This group of proteins consists of about 20 entities, some of which are enzymes. Complement was first associated with the lysis of foreign red blood cells in the nineteenth century it also participates in the lysis of bacterial cells. The complement activation cascade, very similar to the blood coagulation cascade, involves the stepwise activation, via proteolysis, of various components of the complement system until a final protein complex, the membrane attack unit (also called the C5b-9 complex), is generated. It then punches holes in the membrane to which it is bound. 

Caspases are involved in intracellular proteolytic protease activation cascades leading to apoptosis that are initiated by ligands such as tumour necrosis factor (TNF) and Fas ligand. These proteins bind to PM receptors with cytosolic death domains that activate the cas-pase cascades leading to cell death. Caspases are cysteine proteases that cleave peptide bonds on the carboxyl side of aspartate (hence c-asp-ases). 

FIGURE 2,5 Activation cascade involving digiestive erizyines of the Sinai I intestine. The position of the word "entieriokinase on the first reaction arrow indicates that this enzyme activates trypsinogen. 

Figure 8.3 shows a highly schematized view of the activation cascade for the alternative complement pathway upon a microbial membrane surface. The activation steps in the alternative pathway are also shown in Fig. 8.7, which contrasts with the activation steps in the classical complement pathway involving antibody. 

Fig. 8.3 A highly schematized overview of the activation cascade for the alternative complement pathway on a microbial membrane surface. In the presence of a microbial membrane the C3b formed by C3 tickover deposits on the microbial membrane (step A). C3a diffuses away leading to leucocyte activation. The deposited C3b leads to the generation of a stabilized C3 convertase (step B) which, through a positive feedback loop, leads to the amplified cleavage of more C3. Some C3b associates with the C3 convertase to generate a C5 convertase (step C) which will eventually lead to the generation of an...

All human metzincins are secreted as proenzymes. Astacins and adamalysins are mostly activated by calcium-ion-dependent serine proteases pro-protein convertases) that meet up with their substrates in trans-Golgi and secretory vacuoles. These proenzymes are known as furin-like convertases because of their homology to a serine protease called furin and a bacterial endoprotease called subtilisin. The furin-like enzymes require calcium ions to maintain structural stability whereas other serine proteases, represented by trypsin and chymotrypsin, do not. The furin-like pro-protein convertases autocleave their own N-terminal domain propeptide (self-activate) during secretion and then convert the N-terminal domains of co-secreted metzincins. Activation cascades also occur among the... 

G-protein-coupled receptors (GPCRs) react to a wide variety of molecules from some as small as acetylcholine to some as large as the protein SDF-la. Operating on a timescale of minutes to hours, these receptors mediate a plethora of cellular processes. The first reaction in the activation cascade for GPCRs is the binding of the activated receptor to a trimeric complex of proteins called G-proteins (Figure 2.5). These proteins— composed of three subunits named a, (3, and y—act as molecular switches to a number of other effectors in the cell. The binding of activated receptors to the G-protein initiates the dissociation of GDP from the... 

Huang, L.C., Heimark, D., Linko, J., Nolan, R., and Larner, J. A model phosphatase 2C->phosphatase 1 activation cascade via dual control of inhibitor-1 (INH-1) and DARPP-32 dephosphorylation by two inositol glycan putative insulin mediators from beef liver. Biochem. Biophys. Res. Commun., 1999, 255, 150-156. 

The amount of trypsin is much greater than the amount of inhibitor. Why does trypsin inhibitor exist Recall that trypsin activates other zymogens, Consequently, the prevention of even small amounts of trypsin from initiating the inappropriately activated cascade prematurely is vital. Trypsin inhibitor binds to trypsin molecules in the pancreas or pancreatic ducts. Tliis inhibition prevents severe damage to those tissues, which could lead to acute pancreatitis. 

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