Phosphatases activation

Aplastic anemia and leukemia are not the only health effects ascribed to benzene exposure. A number of recent studies have associated benzene exposure with chromosomal changes (aberrations) (118). Other studies have shown abnormalities in porphyrin metabolism and decrease in leucocyte alkaline phosphatase activity in apparendy healthy workers exposed to 10—20 ppm benzene (119,120). Increases in leukoagglutinins, as well as increases in blood fibrinolytic activity, have also been reported and are believed to be responsible for the persistent hemorrhages in chronic benzene poisoning (121,122). 

The development of drugs that block Calcineuiin phosphatase activity has allowed successful prevention of graft rejection. Due to the key role that NFAT has in T-cell activation, these inhibitors behave as potent immunosuppressors. Nevertheless, the important roles that NFAT proteins have in other tissues suggest that exploring the use of similar drugs in other pathological contexts may be clinically and therapeutically relevant. 

The classical PTPs can be subdivided into receptorlike PTPs and nonreceptor, cytosolic PTPs. The second category of PTPs are broadly defined as dual specificity phosphatases (DSPs), which dephosphorylate pSer/ pThr as well as pTyr. MAP kinase phosphatases (MKPs) ( MAP kinase cascades) and PTEN are examples of DSP family members. Remarkably, PTEN also has lipid phosphatase activity that is specific for phosphatidylinositol-3,4,5-trisphosphate generated in response to the actions of PI3K. Finally, the class of low molecular mass (LM-) PTPs and that of CDC25 PTPs accomplish the cells repertoire of PTPs (Fig. 3). 

For in vitro studies there are a number of compounds available to block protein phosphatase activity. Phosphate buffers inactivate all of these enzymes. Several naturally occurring toxins are potent inhibitors of PPPs, e.g., okadaic acid or microcystin, and are frequently used tools. PPM and PTP family members are not affected by these toxins. Vanadate containing solutions are competitive inhibitors of PTPs, pervanadate is an irreversible inhibitor of PTPs. 

Transduction mechanism Inhibition of adenylyl cyclase stimulation of tyrosine phosphatase activity stimulation of MAP kinase activity activation of ERK inhibition of Ca2+ channel activation stimulation of Na+/H+ exchanger stimulation of AM PA/kainate glutamate channels Inhibition of forskol in-stimulated adenylyl cyclase activation of phos-phoinositide metabolism stimulation of tyrosine phosphatase activity inhibition of Ca2+ channel activation activation of K+ channel inhibition of AM PA/ kainate glutamate channels inhibition of MAP kinase activity inhibition of ERK stimulation of SHP-1 and SHP-2 Inhibition of adenylyl cyclase stimulation of phosphoinositide metabolism stimulation of tyrosine phosphatase activation of K+ channel inhibi-tion/stimulation of MAP kinase activity induction of p53 and Bax Inhibition of adenylyl cyclase stimulation of MAP kinase stimulation of p38 activation of tyrosine phosphatase stimulation of K+ channels and phospholipase A2 Inhibition of adenylyl cyclase activation/ inhibition of phosphoinositide metabolism inhibition of Ca2+ influx activation of K+ channels inhibition of MAP kinase stimulation of tyrosine phosphatase... 

Phosphonoacetic acid antiviral activity, 6, 771 Phosphoprotein phosphatases activation... 

Dose and end point used for MRL derivation 0.18 mg/kg/day for increase in serum alkaline phosphatase activity. 

Kim, I.Y., Han, S.Y., and Kang, T.S. et al. (2005). Pyrethroid insecticides, fenvalerate and permethrin, inhibit progesterone-induced alkaline phosphatase activity in T47D human breast cancer cells. Journal of Toxicology and Environmental Health—Part A—Current Issues 68, 2175-2186. 

Inhibitors should be removed from sample. An example is urinary phosphate, which can be removed by dialysis prior to measuring the urinary alkaline phosphatase activity (18). 

Measurement of serum acid phosphatase activities as an aid in the diagnosis and treatment of advanced prostatic carcinoma is based on the observation by Gutman and Gutman that the activity is elevated by skeletal metastases ( ). Many workers have... 

Nodular hyperplasia of the prostate is usually associated with a normal serum acid phosphatase activity. Complications such as acute urinary obstruction or prostatic infarction will elevate this serum activity for several days as will cystoscopy and catheterization (98). Digital palpation of the prostate may result in an elevation which subsides within a few hours. 

Ring, E. J. and Armstrong, A. R. A convenient method for determing serum and bile phosphatase activity. Canad. 

Urinary alkaline phosphatase activity. II. An analytical validation of the assay method. JAMA (1963), 185, 953-957. 

Roos, R. A simplified method for the determination of serum alkaline phosphatase activity. Scand. J. Clin. 

GAO Y H and YAMAGUCHI M (2000) Suppressive effect of genistein on rat bone osteoclasts Involvement of protein kinase inhibition and protein tyrosine phosphatase activation. Int J Mol Med 5, 261-7. 

YAMAGUCHI M and MA z J (2001) Effect of polyphenols on calcium content and alkaline phosphatase activity in rat femoral tissues in vitro. Biol Pharm Bull 24, 1437-9. 

Bioassay for metabolic activity (glycolytic and acid phosphatase activity) of peritoneal-exudative cells after treatment with polysaccharide practions. 

The subcellular location of PG was studied in cells disrupted by osmotic lysis through formation and disruption of sphaeroplasts from self-induced anaerobically-grown cells. A discontinuous sucrose-density gradient produced four bands labelled I, II, III and IV. Band I included many vesicles and a peak of alkaline phosphatase activity (a vacuolar marker in yeasts), NADPH cytochrome c oxidoreductase activity, an endoplasmic reticulum marker, and... 

Definition of Ej and E2 eonformations of the a subunit of Na,K-ATPase involves identification of cleavage points in the protein as well as association of cleavage with different rates of inactivation of Na,K-ATPase and K-phosphatase activities [104,105]. In the Ei form of Na,K-ATPase the cleavage patterns of the two serine proteases are clearly distinct. Chymotrypsin cleaves at Leu (C3), Fig. 3A, and both Na,K-ATPase and K-phosphatase are inactivated in a monoexponential pattern [33,106]. Trypsin cleaves the E form rapidly at Lys ° (T2) and more slowly at Arg (T3) to produce the characteristie biphasic pattern of inactivation. Localization of these splits was determined by sequencing N-termini of fragments after isolation on high resolution gel filtration columns [107]. 

The E2 form is not cleaved by chymotrypsin, but trypsin cleaves at Arg (T1) and subsequently at Lys (T2) and tryptic inactivation of E2K or E2P forms is linear and associated with cleavage at Arg" (Ti) [104,108], Inactivation of K-phosphatase is delayed because cleavage of T1 and T2 in sequence is required for inactivation of K-phosphatase activity [105],... 

Further indications for an additional subunit were provided by a crosslinking analysis of C Eg solubilized H,K-ATPase, which exhibited ATPase and phosphatase activities, and ligand affinities comparable to the native enzyme [70]. Glutar-aldehyde treatment of soluble protein fractions resolved on a linear glycerol gradient revealed no active fraction enriched in monomeric (A/p = 94 kDa) H,K-ATPase. Instead, K -ATPase activity was only obtained in fractions enriched in particles of Mr = 175 kDa. This size also suggested that the functional H,K-ATPase unit is a heterodimer of a catalytic subunit and an additional subunit, since the apparent molecular mass of 175 kDa is probably too small to be a homodimer of the catalytic subunit. 

Like Na,K-ATPase, gastric H,K-ATPase also exhibits a p-nitrophenylphosphatase (/>NPPase) activity. This phosphatase activity is dependent on Mg and K, or one of its congeners with the same order of selectivity as for the ATPase activity, yielding a specific activity of 6D84% of the maximal ATPase activity [4,136,137]. Phosphorylation by pNPP has not been demonstrated and transport is also not catalyzed by this substrate. As in the ATPase reaction the effect of on the... 

Some haloperoxidases contain vanadium and a review of vanadium peroxidases has been given (Butler 1998). The structure of the vanadium enzyme in the terrestrial fungus Cur-vularia inaequalis has been determined by x-ray analysis (Messerschmidt et al. 1997), and the apochloroperoxidase possesses, in addition, phosphatase activity that can be rationalized on the basis of the isomorphism of phosphate and vanadate (Renirie et al. 2000). 

Renirie R, W Hemrika, R Wever (2000) Peroxidase and phosphatase activity of active-site mutants of vanadium chloroperoxidase from the fungus Curvularia inaequalis. J Biol Chem 275 11650-11657. 

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