Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma membrane proteolipid (plasmolipin), which was originally isolated from kidney membranes, has also been shown to be present in brain. In this study, we examined the distribution of plasmolipin in brain regions, myelin, and oligodendroglial membranes. Immunoblot analysis of different brain regions revealed that plasmolipin levels were higher in regions rich in white matter. Plasmolipin was also detected in myelin, myelin subfractions, and oligodendroglial membranes. Immunocytochemical analysis of the cerebellum revealed that plasmolipin was localized in the myelinated tracts. Plasmolipin levels in myelin were enriched during five successive cycles of myelin purification, similar to the enrichment of myelin proteolipid apoprotein (PLP) and myelin basic protein (MBP). In contrast, levels of Na+,K(+)-ATPase and a 70-kDa protein were decreased. When myelin or white matter was extracted with chloroform/methanol, it contained, in addition to PLP, a significant amount of plasmolipin. Quantitative immunoblot analysis suggested that plasmolipin constitutes in the range of 2.2-4.8% of total myelin protein. Plasmolipin, purified from kidney membranes, was detected by silver stain on gels at 18 kDa and did not show immunological cross-reactivity with either PLP or MBP. Thus, it is concluded that plasmolipin is present in myelin, possibly as a component of the oligodendroglial plasma membrane, but is structurally and immunologically different from the previously characterized myelin proteolipids.
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PMID:Presence of the plasma membrane proteolipid (plasmolipin) in myelin. 169 42

Myelin basic protein (MBP) binds to both skeletal muscle and brain tropomyosin resulting in the formation of paracrystalline tactoids in the absence of divalent cations and at neutral pH. Both types of tropomyosin reduce the inhibition of the ATPase activity of actomyosin caused by MBP. On the other hand, MBP alters the effect of both brain and skeletal muscle tropomyosins on the actomyosin ATPase, even though MBP and tropomyosin bind independently to actin. We conclude that MBP cannot substitute for troponin I in the regulation of the action of tropomyosin on actin.
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PMID:Interaction of tropomyosin with myelin basic protein and its effect on the ATPase activity of actomyosin. 243 9

The effect of essential fatty acid (EFA) deficiency on the activities of several membrane-bound enzymes was examined in the brains of C57BL/6J mice. Pregnant females were placed on an EFA-deficient diet during the last week of gestation and their progeny were examined at intervals up to 16 weeks after birth. Early signs of the deficiency, such as reduced body and brain weight, were noted in the mice on the experimental diet. The fatty acid ratio of 20:3w9/20:4w6, a biochemical index of EFA deficiency, rose progressively in the deficient brains from 0.17 at 4 weeks to 0.68 at 16 weeks. Only one of the membrane-bound enzymes studied, i.e. ATPase, demonstrated any consistent significant alteration in specific activity as a consequence of the deficiency. The accumulation of myelin, as measured by the levels of myelin basic protein, was reduced from the earliest age studied. These findings suggest that EFA deficiency does not exert a general, nonspecific effect on all membranes in the brain and that hypomyelination is a major effect of EFA deficiency on brain development.
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PMID:Effects of essential fatty acid deficiency on mouse brain development. 244 48

A disorder of CNS myelination was found in paralytic tremor ("pt") rabbits. The condition is inherited in a sex-linked recessive mode. Ultrastructurally, an obvious myelin deficiency with aberration of myelin sheath formation is observed. The yield of myelin isolation was reduced to 20-30% of control. Myelin isolated from 4-week-old "pt" rabbits contained reduced amounts of galactosphingolipids and of several myelin protein markers. Moreover, myelin basic protein, analyzed by two-dimensional gel electrophoresis, showed a deficit in its more basic components. All these facts suggest a delay in myelin maturation. Ganglioside content was increased as well as Na+,K+-ATPase specific activity. 2',3'-Cyclic nucleotide phosphodiesterase (CNPase) specific activity was the same in "pt" as in control myelin but differed by having greater sensitivity to detergent activation.
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PMID:Myelin composition and activities of CNPase and Na+,K+-ATPase in hypomyelinated "pt" mutant rabbit. 282 82

The cerebellar hypoplasia induced by hereditary hyperbilirubinemia in the Gunn rat was analyzed neurochemically and immunohistochemically. The antiserum against myelin basic protein was used to visualize the arborization of the fibers in the cerebellum. Arborization was very scarce in the affected lobes of the homozygous (jj) cerebellum. Na,K-ATPase activity did not show significant differences between the jj and the control (Jj) cerebellum. The concentration of norepinephrine in the jj cerebellum was about 1.5 times that of the control. However, the activation ratio of the Na,K-ATPase by norepinephrine and other catecholamines such as dopamine and isoproterenol was about twice as high as the basal activity, and no significant difference was observed between the jj and the Jj cerebella. The glutamic acid decarboxylase activity of the jj cerebellum did not differ significantly from that of the control.
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PMID:Neurochemical studies on the cerebellar hypoplasia of Gunn rat (hereditary hyperbilirubinemic rat). 628 59

Autotaxin (ATX) is an extracellular enzyme and an autocrine motility factor that stimulates pertussis toxin-sensitive chemotaxis in human melanoma cells at picomolar to nanomolar concentrations. This 125-kDa glycoprotein contains a peptide sequence identified as the catalytic site in type I alkaline phosphodiesterases (PDEs), and it possesses 5'-nucleotide PDE (EC 3.1.4.1) activity (Stracke, M. L., Krutzsch, H. C., Unsworth, E. J., Arestad, A., Cioce, V., Schiffmann, E., and Liotta, L. (1992) J. Biol. Chem. 267, 2524-2529; Murata, J., Lee, H. Y., Clair, T., Krutsch, H. C., Arestad, A. A., Sobel, M. E., Liotta, L. A., and Stracke, M. L. (1994) J. Biol. Chem. 269, 30479-30484). ATX binds ATP and is phosphorylated only on threonine. Thr210 at the PDE active site of ATX is required for phosphorylation, 5'-nucleotide PDE, and motility-stimulating activities (Lee, H. Y., Clair, T., Mulvaney, P. T., Woodhouse, E. C., Aznavoorian, S., Liotta, L. A., and Stracke, M. L. (1996) J. Biol. Chem. 271, 24408-24412). In this article we report that the phosphorylation of ATX is a transient event, being stable at 0 degrees C but unstable at 37 degrees C, and that ATX has adenosine-5'-triphosphatase (ATPase; EC 3.6.1.3) and ATP pyrophosphatase (EC 3.6.1.8) activities. Thus ATX catalyzes the hydrolysis of the phosphodiester bond on either side of the beta-phosphate of ATP. ATX also catalyzes the hydrolysis of GTP to GDP and GMP, of either AMP or PPi to Pi, and the hydrolysis of NAD to AMP, and each of these substrates can serve as a phosphate donor in the phosphorylation of ATX. ATX possesses no detectable protein kinase activity toward histone, myelin basic protein, or casein. These results lead to the proposal that ATX is capable of at least two alternative reaction mechanisms, threonine (T-type) ATPase and 5'-nucleotide PDE/ATP pyrophosphatase, with a common site (Thr210) for the formation of covalently bound reaction intermediates threonine phosphate and threonine adenylate, respectively.
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PMID:Autotaxin is an exoenzyme possessing 5'-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. 899 94

The p21-activated kinase (PAK) family includes protein phosphotransferases regulated by the GTPases rho, rac, and cdc42. Sequence homology, activation mechanism, and substrate specificity suggest that the well-characterized human placenta S6/H4 kinase is a member of this family. In these studies, S6/H4 kinase purified to homogeneity from human placenta was activated in vitro by cdc42-GTP, or protease incubation and MgATP-dependent autophosphorylation. The cdc42-activated enzyme demonstrated an Mr 60,000, and shares sequence homology with the gammaPAK family. Antipeptide antibodies against one of the autophosphorylation site sequences recognized a single p60 protein in the purified placenta preparation or Jurkat cell extracts. An autophosphorylated Mr 40,000 protein, previously identified as the catalytic domain of the enzyme, was also detected by the antibody after protease activation. Crude PAK60 obtained from Mono Q chromatography of Jurkat cell extracts and purified placenta enzyme catalyzed phosphorylation of histone H4 and myelin basic protein as well as a variety of synthetic peptides previously identified as S6/H4 kinase substrates. In addition, Jurkat myosin II and the regulatory myosin light chain were phosphorylated by the Jurkat and placenta gammaPAK. Synthetic peptides were used to demonstrate that the site of light chain phosphorylation occurs at the serine which results in ATPase activation. The data suggest that human gammaPAK may regulate cell motility by a GTP-dependent and calcium-independent mechanism.
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PMID:Myosin phosphorylation by human cdc42-dependent S6/H4 kinase/gammaPAK from placenta and lymphoid cells. 939 38

JS 3/16, derived from passaged oligodendroglial cultures prepared from rat cerebral white matter, differentiate from progenitors (OP) into complex process-bearing, galactocerebroside-positive but myelin basic protein-negative immature oligodendrocyte-like cells (ImO) after withdrawal of trophic factors. We found that JS 3/16 ImO are markedly more susceptible than OP to cell death after sustained alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptor (AMPA-GluR) activation. This excitotoxicity is preceded by loss of intracellular Ca(2+) homeostasis, which is more marked in ImO than OP. We identified three factors likely to contribute to the diminished Ca(2+) homeostatic capacity of ImO. First, signal intensities of immunoreactive GluR2, GluR3, and GluR4 AMPA-GluR subunits are increased 1.3- to 2.2-fold in ImO over OP without comparable changes in RNA editing and alternative splicing. Second, transcriptional levels of genes encoding Na(+)-Ca(2+) exchanger proteins and a plasma membrane ATPase (PMCA1), which are necessary for Ca(2+) extrusion across the plasma membrane, are lower in ImO than in OP. Third, ImO have more depolarized basal mitochondrial membrane potential (Delta Psi) than OP, and Delta Psi collapses within 15 min after onset of AMPA-GluR activation in almost all ImO, but not in the majority of OP. This Delta Psi collapse limits the capacity of ImO mitochondria to buffer the rise in intracellular Ca(2+) caused by AMPA-GluR activation. The JS 3/16 line provides a valuable system for analysis of intracellular Ca(2+) homeostasis and AMPA-GluR-mediated excitotoxicity in the oligodendroglial lineage.
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PMID:Diminished calcium homeostasis and increased susceptibility to excitotoxicity of JS 3/16 progenitor cells after differentiation to oligodendroglia. 1087 3

The mitogen-activated protein (MAP) kinases are characterized by their requirement for dual phosphorylation at a conserved threonine and tyrosine residue for catalytic activation. The structural consequences of dual-phosphorylation in the MAP kinase ERK2 (extracellular signal-regulated kinase 2) include active site closure, alignment of key catalytic residues that interact with ATP, and remodeling of the activation loop. In this study, we report the specific effects of dual phosphorylation on the individual catalytic reaction steps in ERK2. Dual phosphorylation leads to an increase in overall catalytic efficiency and turnover rate of approximately 600,000- and 50,000-fold, respectively. Solvent viscosometric studies reveal moderate decreases in the equilibrium dissociation constants (K(d)) for both ATP and myelin basic protein. However, the majority of the overall rate enhancement is due to an increase in the rate of the phosphoryl group transfer step by approximately 60,000-fold. By comparison, the rate of the same step in the ATPase reaction is enhanced only 2000-fold. This suggests that optimizing the position of the invariant residues Lys(52) and Glu(69), which stabilize the phosphates of ATP, accounts for only part of the enhanced rate of phosphoryl group transfer in the kinase reaction. Thus, significant stabilization of the protein phosphoacceptor group must also occur. Our results demonstrate similarities between the activation mechanisms of ERK2 and the cell cycle control enzyme, Cdk2 (cyclin-dependent kinase 2). Rather than dual phosphorylation, however, activation of the latter is controlled by cyclin binding followed by phosphorylation at Thr(160).
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PMID:Mechanism of activation of ERK2 by dual phosphorylation. 1101 42

Although MAG-null mice myelinate relatively normally except for subtle structural abnormalities in the periaxonal region of myelin sheaths, they develop more severe pathological changes as they age. The purpose of this study was to further define the biochemical aspects of CNS pathology caused by an absence of MAG. Proteins associated with myelin and oligodendrocytes were quantified by densitometry of western blots in whole brain homogenates, as well as in isolated myelinated axons and myelin. Neither myelin yields, nor levels of myelin basic protein and proteolipid protein, were decreased in comparison to control levels in 14-month-old MAG-null mice. On the other hand, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and the 120 kD neural cell adhesion molecule (N-CAM) were substantially reduced in whole brain, myelinated axons, and myelin. Tubulin, Na(+)K(+)ATPase and Fyn tyrosine kinase were also reduced significantly in myelin-related fractions, but not in whole brain homogenate. The decreased levels of these proteins suggest pathological abnormalities in oligodendrocytes. Furthermore, significant reductions of CNPase and 120 kD NCAM were also present at 2 months, indicating that the oligodendroglial abnormalities begin at a relatively early age. Neither TUNEL assays nor multiplex RT-PCR for mRNAs of apoptosis-related proteins in the aging MAG-null mice provided evidence for apoptotic oligodendrocytes. These biochemical findings suggest oligodendroglial damage in MAG-null mice and support the morphological observations pointing to a progressive "dying-back oligodendrogliopathy" as a consequence of MAG deficiency.
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PMID:Oligodendrocytes in aging mice lacking myelin-associated glycoprotein are dystrophic but not apoptotic. 1110 61


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