Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We show here that a protein tyrosine phosphatase inhibitor, sodium orthovanadate, induces rat pheochromocytoma cells to express neurites, a prominent morphological marker of neuronal phenotype. Vanadate-induced differentiation and neurite outgrowth in pheochromocytoma cells was not as extensive as that induced by the positive control employed, nerve growth factor. However, neurite outgrowth responses were comparable between nerve growth factor-treated pheochromocytoma cells and cells primed and then restimulated with vanadate. In the human neuroblastoma cell line, SH-SY5Y, a single exposure to vanadate induced neurite extension in this cell line equal to that initiated by nerve growth factor. In both cell lines vanadate treatment resulted in tyrosine phosphorylation of several high-molecular-weight proteins and using anti-phosphotyrosine antibodies, intense fluorescence was observed in the cell body and neurites of pheochromocytoma cells exposed to vanadate. Vanadate mediated differentiation and neurite outgrowth in pheochromocytoma cells could be ablated by the tyrosine kinase inhibitor erbastatin, whereas nerve growth factor-induced neurite outgrowth was only partially inhibited. In SH-SY5Y cells, erbstatin mediated partial inhibition of both vanadate and nerve growth factor-induced neurite elongation with similar kinetics. In contrast, K252b, a trk tyrosine kinase inhibitor, exhibited only a 30% reduction of neurite outgrowth in vanadate treated pheochromocytoma cells but an 80% reduction in nerve growth factor-treated cells. In SH-SY5Y cells, K252a did not have a statistically significant effect on neurite elongation induced by vanadate in contrast to a 60% reduction in nerve growth factor-treated cells. The membrane impermeable analogue K252b, had no effect on neurite elongation induced with either vanadate or nerve growth factor in these cells. The effects of vanadate were not mimicked by ouabain (0.1-50 microM) indicating that vanadate does not induce differentiation and/or neurite extension by inhibiting ion channel Na,K-ATPase, which is one of its other well-characterised inhibitory activities. Evidence for the selective action of vanadate on some but not all neuronal cell lines comes from the fact that it did not induce neurite extension in the human neuroblastoma cell line SK-N-MC. These data imply that vanadate-induced neurite outgrowth responses in pheochromocytoma and SH-SY5Y cells can be induced by the inhibition of tyrosine phosphatases and appears not to simply mimic nerve growth factor signals. The target(s) of vanadate action in the two cell lines are currently being sought.
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PMID:Vanadate stimulates differentiation and neurite outgrowth in rat pheochromocytoma PC12 cells and neurite extension in human neuroblastoma SH-SY5Y cells. 752 Oct 24

We show that PTP1D, a protein tyrosine phosphatase that contains two SH2 domains, is preferentially expressed in slow skeletal muscle fibers. Immunohistochemical staining using polyclonal antibodies against PTP1D demonstrated that PTP1D was expressed in a subpopulation of rodent muscle fibers. These fibers were identified as slow Type I fibers based on histochemical ATPase assays and slow myosin heavy chain expression. Northern and Western analyses showed that PTP1D levels were higher in predominantly slow muscles than in predominantly fast muscles. This differential expression of PTP1D in slow muscle fibers appeared by birth. In cultures of mouse myogenic cells, PTP1D was expressed after MyoD and myogenin and appeared in myotubes derived from embryonic, fetal, and postnatal myoblasts. Remarkably, PTP1D was organized into sarcomeres in a pattern coincident with myosin heavy chain, suggesting that PTP1D associates with a component of the thick filament. These results show that PTP1D is preferentially expressed in slow muscle fibers. We speculate that PTP1D may play a role in slow muscle fiber function and differentiation.
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PMID:Differential expression of PTP1D, a protein tyrosine phosphatase with two SH2 domains, in a slow and fast skeletal muscle fibers. 861 15

We have used RNA differential display to identify specific mRNA species that are regulated by interferon-gamma (IFN gamma) treatment of enriched astrocyte cultures. Following a 24-hour treatment with IFN, mRNA was subjected to differential display using 15 different random primers. 105 upregulated and 5 downregulated cDNAs were selected for further sequencing and identification. Northern blot analysis confirmed the upregulation of 13 genes identical or highly similar to: intercrine adrenomedullin, H-rev 107, CAP-like protein, ATP synthase epsilon-subunit, complement C3, S-100 beta, Ca2+ ATPase, mg11, IFN-upregulated 56-kD protein mRNA, laminin receptor-like protein, protein tyrosine phosphatase, and zic. These data suggest that exposure to IFN gamma results in a complex change in the pattern of astrocyte gene expression.
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PMID:Identification of mRNAs regulated by interferon-gamma in cultured rat astrocytes by PCR differential display. 884 Mar 37

mRNA capping requires the sequential action of three enzymatic activities: RNA triphosphatase, guanylyl-transferase, and methyltransferase. Here we characterize a gene (CEL-1) believed to encode the C. elegans capping enzyme. CEL-1 has a C-terminal domain containing motifs found in yeast and vaccinia virus capping enzyme guanylyltransferases. The N-terminal domain of CEL-1 has RNA triphosphatase activity. Surprisingly, this domain does not resemble the vaccinia virus capping enzyme but does have significant sequence similarity to the protein tyrosine phosphatase (PTP) enzyme family. However, CEL-1 has no detectable PTP activity. The mechanism of the RNA triphosphatase is similar to that of PTPs: the active site contains a conserved nucleophilic cysteine required for activity. These results broaden the superfamily of PTP-like phosphatases to include enzymes with RNA substrates.
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PMID:An RNA 5'-triphosphatase related to the protein tyrosine phosphatases. 920 Jun 5

The superfamily of protein tyrosine phosphatases (PTPs) includes at least one enzyme with an RNA substrate. We recently showed that the RNA triphosphatase domain of the Caenorhabditis elegans mRNA capping enzyme is related to the PTP enzyme family by sequence similarity and mechanism. The PTP most similar in sequence to the capping enzyme triphosphatase is BVP, a dual-specificity PTP encoded by the Autographa californica nuclear polyhedrosis virus. Although BVP previously has been shown to have modest tyrosine and serine/threonine phosphatase activity, we find that it is much more potent as an RNA 5'-phosphatase. BVP sequentially removes gamma and beta phosphates from the 5' end of triphosphate-terminated RNA, leaving a 5'-monophosphate end. The activity was specific for polynucleotides; nucleotide triphosphates were not hydrolyzed. A mutant protein in which the active site cysteine was replaced with serine was inactive. Three other dual-specificity PTPs (VH1, VHR, and Cdc14) did not exhibit detectable RNA phosphatase activity. Therefore, capping enzyme and BVP are members of a distinct PTP-like subfamily that can remove phosphates from RNA.
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PMID:A protein tyrosine phosphatase-like protein from baculovirus has RNA 5'-triphosphatase and diphosphatase activities. 970 57

Mammalian capping enzymes are bifunctional proteins with both RNA 5'-triphosphatase and guanylyltransferase activities. The N-terminal 237-aa triphosphatase domain contains (I/V)HCXXGXXR(S/T)G, a sequence corresponding to the conserved active-site motif in protein tyrosine phosphatases (PTPs). Analysis of point mutants of mouse RNA 5'-triphosphatase identified the motif Cys and Arg residues and an upstream Asp as required for activity. Like PTPs, this enzyme was inhibited by iodoacetate and VO43- and independent of Mg2+, providing additional evidence for phosphate removal from RNA 5' ends by a PTP-like mechanism. The full-length, 597-aa mouse capping enzyme and the C-terminal guanylyltransferase fragment (residues 211-597), unlike the triphosphatase domain, bound poly (U) and were nuclear in transfected cells. RNA binding was increased by GTP, and a guanylylation-defective, active-site mutant was not affected. Ala substitution at positions required for the formation of the enzyme-GMP capping intermediate (R315, R530, K533, or N537) also eliminated poly (U) binding, while proteins with conservative substitutions at these sites retained binding but not guanylyltransferase activity. These results demonstrate that the guanylyltransferase domain of mammalian capping enzyme specifies nuclear localization and RNA binding. Association of capping enzyme with nascent transcripts may act in synergy with RNA polymerase II binding to ensure 5' cap formation.
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PMID:Mammalian capping enzyme binds RNA and uses protein tyrosine phosphatase mechanism. 977 Apr 68

Phosphatidylserine synthesis as measured by the incorporation of [(3)H]serine into phosphatidylserine (PtdSer) through the serine-base exchange enzyme system (serine-BEES) is markedly inhibited in Jurkat cells treated with caffeine. The caffeine-induced inhibition was compared to that observed in cells treated with either CD3 mAb or thapsigargin. While CD3- and thapsigargin-induced inhibition was related to the release of Ca(2+) from the endoplasmic reticulum (ER), a process that deprives the serine-BEES of its major cofactor, caffeine modified PtdSer synthesis in the absence of decreased Ca(2+) content of ER. Using Jurkat clones differing by the expression of cell surface markers or protein tyrosine kinases implicated in the CD3/TCR signal transmission pathway, we have shown that CD3 mAb-induced inhibition of PtdSer synthesis necessitates the expression of both the CD3/TCR and the protein tyrosine phosphatase CD45 at the cell surface as well as the presence of p56(lck) and ZAP-70 protein tyrosine kinases. By contrast, thapsigargin, a blocker of the Ca(2+)-ATPase of the ER, known for its Ca(2+) releasing properties, inhibited PtdSer synthesis in all the Jurkat clones tested, indicating that this compound bypasses the CD3/TCR-induced signals. Despite its lack of effect on Ca(2+) release from ER and on protein tyrosine phosphorylations, caffeine inhibited PtdSer synthesis in all the Jurkat clones. The use of several cAMP-inducing drugs and of others xanthine derivatives indicated that caffeine modify PtdSer synthesis either by a direct action on the serine-BEES or by a modification of the structure of the phospholipids used as substrate by the enzyme.
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PMID:Regulation of phosphatidylserine synthesis in Jurkat T cell clones: caffeine bypasses CD3/TCR-induced protein tyrosine kinases and calcium signals. 1060 May 31

Follicle-stimulating hormone (FSH) controls the development of follicle-enclosed oocytes in the mammalian ovary by interacting with specific receptors located exclusively on granulosa cells. Its biological activity involves stimulation of intercellular communication, intracellular signaling, and up-regulation of steroidogenesis; the entire spectrum of genes regulated by FSH is not yet fully characterized. We have established monoclonal rat FSH-responsive granulosa cell lines that express FSH receptors at 20-fold higher rates than with primary cells, and thus increased the probability of yielding a distinct spectrum of genes modulated by FSH. Using Affymetrix DNA microarrays, we discovered 11 genes not reported earlier to be up-regulated by FSH and 9 genes not reported earlier to be down-regulated by FSH. Modulation of signal transduction associated with G-protein signaling, phosphorylation of proteins, and intracellular-extracellular ion balance was suggested by up-regulation of decay accelerating factor GPI-form precursor (DAF), membrane interacting protein RGS16, protein tyrosine phosphatase (PTPase), oxidative stress-inducible protein tyrosine phosphatase (OSIPTPase), and down-regulation of rat prostatic acid phosphatase (rPAP), Na+, K+-ATPase, and protein phosphatase 1beta. Elevation in granzyme-like proteins 1 and 3, and natural killer (NK) cell protease 1 (NKP-1) along with reduction in carboxypeptidase E indicates possible FSH-mediated preparation of the cells for apoptosis. Up-regulation of vascular endothelial growth factors indicates the ability of FSH to produce angiogenic factors upon their maturation; whereas, reduction in insulin-like growth factor binding protein (IGFBP3) indicates its increased potential to promote p53-induced apoptosis. Striking similarities in FSH modulation of gene expression were found in primary cultures of human granulosa cells obtained from IVF patients although these cells expressed only 1% of FSH receptor compared with immortalized rat cells, as indicated by microarray technique, which probably is in the normal range of expression of this receptor in nontransformed cells. These findings should increase our understanding of the mechanism of FSH action in stimulating development of the ovarian follicular cells, of intracellular and intercellular communication, and of increasing the potential of ovarian follicular cells to undergo apoptosis during the process of selection of the dominant follicle.
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PMID:Novel genes modulated by FSH in normal and immortalized FSH-responsive cells: new insights into the mechanism of FSH action. 1283 90

The abnormal sodium content of many cataracts suggests Na,K-ATPase is vital for maintenance of eye lens transparency. Since tyrosine phosphorylation is considered a possible regulatory mechanism for Na,K-ATPase, experiments were conducted to test the influence of protein tyrosine phosphatase-1B (PTP-1B) on Na,K-ATPase activity. Membrane material was isolated separately from porcine lens epithelium and fiber cells. Tyrosine phosphoproteins, Na,K-ATPase alpha1 polypeptide and PTP-1B were examined by Western blot. Na,K-ATPase activity was determined by measuring ATP hydrolysis in the presence or absence of ouabain. Western blot analysis revealed tyrosine phosphorylation of multiple membrane proteins in both lens cell types, the differentiated fiber cells and non-differentiated epithelium. When membrane material was subjected to immunoprecipitation using an antibody directed against Na,K-ATPase alpha1, a colocalized phosphotyrosine band was detected in lens fibers but not epithelium. Incubation with PTP-1B caused a approximately 50% increase of Na,K-ATPase activity in fiber membrane material. Na,K-ATPase activity in lens epithelium membrane material was not significantly altered by PTP-1B treatment even though PTP-1B was demonstrated to cause dephosphorylation of multiple membrane proteins in the epithelium as well as fibers. While endogenous PTP-1B was detected in both cell types, endogenous tyrosine phosphatase activity was low in both epithelium and fiber membrane material. The results illustrate endogenous tyrosine phosphorylation of Na,K-ATPase alpha1 polypeptide in fibers. Na,K-ATPase alpha1 in lens fibers may be a potential target for PTP-1B.
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PMID:The influence of protein tyrosine phosphatase-1B on Na,K-ATPase activity in lens. 1525 64

The tyrosine phosphatase PTP-MEG2 is targeted by its amino-terminal Sec14p homology domain to the membrane of secretory vesicles. There it regulates vesicle size by promoting homotypic vesicle fusion by a mechanism that requires its catalytic activity. Here, we identify N-ethylmaleimide-sensitive factor (NSF), a key regulator of vesicle fusion, as a substrate for PTP-MEG2. PTP-MEG2 reduced the phosphotyrosine content of NSF and co-localized with NSF and syntaxin 6 in intact cells. Furthermore, endogenous PTP-MEG2 co-immunoprecipitated with endogenous NSF. Phosphorylation of NSF at Tyr 83, as well as an acidic substitution at the same site, increased its ATPase activity and prevented alphaSNAP binding. Conversely, expression of a Y83F mutant of NSF caused spontaneous fusion events. Our results suggest that the molecular mechanism by which PTP-MEG2 promotes secretory vesicle fusion involves the local release of NSF from a tyrosine-phosphorylated, inactive state. This represents a novel mechanism for localized regulation of NSF and the first demonstrated role for a protein tyrosine phosphatase in the regulated secretory pathway.
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PMID:Control of vesicle fusion by a tyrosine phosphatase. 1532 54


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