Pathways for Activation

PI-PLC activation by EGF is initiated by the binding of EGF to its specific receptors containing sites auto-phosphorylated by their intrinsic tyrosine kinase. The autophosphorylated site of the receptor then interacts with the SH2 domain of PI-PLC-y (Rhee and Choi, 1992a Exton, 1994), and PI-PLC-y will be activated as a consequence of its tyrosine phosphorylation. This results in IP3 and DA(S release from PIP2. 

There are potential roles that different isoforms of G-protein responsive PI-PLC might fill. One might be to provide a unique response in specific tissues or cells. It is possible that specific distribution of PI-PLC-p 

Two inhibitors are known. (1) Neomycin is an antibiotic that interacts with polyphosphoinositides. Neomycin inhibited the Ca2+-dependent histamine secretion from GTPyS-loaded mass cells (Cockcroft and Gomperts, 1985), the GTPyS-induced contractions in skinned rabbit main pulmonary arteries (Kobayashi et al., 1988), the carbachol-induced contractions in 

A correlation between smooth muscle stimulation and increased metabolism of inositol phosphates has been known for some time, for example, in carbachol-or NE-stimulated rabbit iris (Abdel-Latif et al, 1977), in carbachol- or ACh-stimulated trachea (Baron et al., 1984 Hashimoto et al., 1985 Takuwa et al., 1986 Duncan et al., 1987), in angiotensin- or vasopressin-stimulated vascular muscle (Smith et al., 1984 Doyle and Ruegg, 1985), in ACh- or histamine-stimulated visceral muscle (Best et al, 1985), in oxytocin-stimulated human myometrium (Amiot etal., 1993), or in bombesin-stimulated rat myometrium (Schrey etal., 

established that receptor activation in smooth muscle is coupled to an enhanced inositol phosphate metabolism. The accumulation of inositol phosphates was not controlled by either the extracellular or intracellular Ca2+ concentration, in agreement with the pharmacomechanical coupling mechanism (Somlyo and Somlyo, 1968). 

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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. 

Anderson, N. G., Mailer, J. L., and Tonks, N. K. (1990b). Requirement for the integration of signals from two distinct phosphorylation pathways for activation of MAPkinase. Nature 34 3651-3653. 

Oubrahim, H., Richard, J.M., Cantin-Esnault, D. (1998). Peroxidase-mediated oxidation, a possible pathway for activation of the fungal nephrotoxin orellanine and related compounds. ESR and spin-trapping studies, Free Radic. Res., 28, 497-505. 

Figure 17.6 A summaiy of the three pathways for activation of complement. See text for details.

Activation of MEK kinases occurs particularly via proteins of the Ras superfamUy (p21-Ras, Rho/Rac proteins). However, other pathways for activation of MEK kinases, e.g., via other protein kinases such as protein kinase C or PAK (p21 activated kinase) (review Marshall, 1995 Robinson and Cobb, 1997) have also been reported. 

Szeto, W.W. Nixon, B.T. Ronson, C.W. Ausubel, EM. Identification and characterization of the Rhizobium meliloti ntrC gene R. meliloti has separate regulatory pathways for activation of nitrogen fixation genes in free-living and symbiotic cells. J. BacterioL, 169, 1423-1432 (1987)... 

Complement is a group of more than 30 proteins found in blood serum, which are activated in a cascade mechanism when antibody and antigen com-bine10/111/142 148 (Eq. 31-1). This classical pathway for activation of complement is outlined in Fig. 31-8. The proteins involved in the cascade are designated Cl to C9. Many of them undergo proteolytic cleavage, the... 

Figure 31-8 Pathways for activation of the complement system. Active proteases are designated by abbreviations in boldface.

The usual substitution pathway for activated olefins is illustrated by Scheme 34 regarding anionic nucleophiles. In 73, R1 and R2 are electron-attracting groups L is the leaving group (usually a halogen atom) and Y is the charged nucleophile (in particular, alkoxides and thioalkoxides). 

Figure 1. Metabolic pathways for activation of DMBA. MFO, mixed function oxidase EH, epoxide hydrase.

Figure 5. Schematic arrangement of the surface of a partly crystallized E-L TM amorphous alloy such as Pd-Zr. A matrix of zirconia consisting of the two polymorphs holds particles of the L transition metal (Pd) which are structured in a skin of solid solution with oxygen (white) and a nucleus of pure metal (black). The arrows indicate transport pathways for activated oxygen either through bulk diffusion or via the top surface. An intimate contact with a large metal-to-oxide interface volume with ill-defined defective crystal structures (shaded area) is essential for the good catalytic performance. The figure is compiled from the experimental data in the literature [26, 27].

Scheme 4 Proposed pathways for activation of HOOH by Fe Cl3in MeCN...

An observation made by Lehninger et al. in 1978 [98] showed that Ca " -preloaded mitochondria from various tissues released Ca " in response to the addition of acetoacetate or oxaloacetate. The release was reversed by a subsequent addition of )8-hydroxybutyrate. The interpretation of this phenomenon was that the redox state of pyridine nucleotides controlled the rate of entry and exit of Ca, thus regulating its concentration in the external medium. In the experiment, mitochondria were maintained in an energized state throughout the experiment by the addition of succinate plus rotenone or other pyridine nucleotide-independent substrates. The phenomenon observed was not ruthenium red-sensitive, suggesting that the efflux pathway for activated by the shift in pyridine nucleotide redox state was... 

ANIXRS0NNG,MALLERJL,T0NKSNK, STURGIU,TW. Requirements few integration of signals from two distind phosphorylation pathways for activation of MAP kinase. Nature343 651-653,1990. 

O Malley BW, Schrader WT, Mani S, Smith C, Weigel NL, et al. 1995. An alternative ligand-independent pathway for activation of steroid receptors. Recent Prog. Horm. Res. 50 333 17... 

Satou M, Mori K, Tazawa Y, Takagi SF. 1983c. Neuronal pathways for activation of inhibitory intemeurons in pyriform cortex of the rabbit. J Neurophysiol 50 74-88. 

Russo T, Zambrano N, Esposito F, Ammedol R, Cimino F, Fiscella M, Jackman J, O Connor PM, Anderson ON, Appella E. A p53-independent pathway for activation of WAF1/CIP1 expression following oxidative stress. J Biol Chem 1995 270 29386-29391. 

It seems to be evident that the ionic pathway for active transport is different from those for action currents which are predominantly an exchange of Na" and due to their electrochemical potential gradients (Figure 36). It is very likely that there is more than one ionic path responsible for the action currents, and that these paths are to some extent specific for each ionic species (such as Na" channels and channels and Ca " channels, etc.), since the ionic current through each channel can be almost completely suppressed... 

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