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

---

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

Virulence effectors delivered into intestinal epithelial cells by Salmonella trigger actin remodeling to direct pathogen internalization and intracellular replication in Salmonella-containing vacuoles (SCVs). One such effector, SptP, functions early during pathogen entry to deactivate Rho GTPases and reverse pathogen-induced cytoskeletal changes following uptake. SptP also harbors a C-terminal protein tyrosine phosphatase (PTPase) domain with no clear host substrates. Investigating SptP's longevity in infected cells, we uncover a late function of SptP, showing that it associates with SCVs, and its PTPase activity increases pathogen replication. Direct SptP binding and specific dephosphorylation of the AAA+ ATPase valosin-containing protein (VCP/p97), a facilitator of cellular membrane fusion and protein degradation, enhanced pathogen replication in SCVs. VCP and its adaptors p47 and Ufd1 were necessary for generating Salmonella-induced filaments on SCVs, a membrane fusion event characteristic of the pathogen replicative phase. Thus, Salmonella regulates the biogenesis of an intracellular niche through SptP-mediated dephosphorylation of VCP.
...
PMID:The Salmonella effector SptP dephosphorylates host AAA+ ATPase VCP to promote development of its intracellular replicative niche. 1928 32

Modulation of the physiologically influential Na(+),K(+)-ATPase is a complex process involving a wide variety of factors. To determine the possible effects of the protein tyrosine phosphatase (PTP) inhibitors dephostatin and Et-3,4-dephostatin on human and pig, renal cells and enzymatic extracts, we treated our samples (15 min-24 h) with those PTP inhibitors (0-100 microM). PTP inhibitors were found to possess a concentration-dependent inhibition of Na(+),K(+)-ATPase activity in both human and pig samples. The inhibition was similarly demonstrated on all cellular, microsomal fraction and purified Na(+),K(+)-ATPase levels. Despite rigorous activity recovery attempts, the PTP inhibitors' effects were sustained on Na(+),K(+)-ATPase activity. Western blotting experiments revealed the expression of both alpha(1)- and beta(1)-subunits in both human and pig tissues. alpha(1)-Subunits possessed higher tyrosine phosphorylation levels with higher concentrations of PTP inhibitors. Meanwhile, serine/threonine residues of both alpha(1)- and beta(1)-subunits demonstrated diminished phosphorylation levels upon dephostatin treatment. Accordingly, we provide evidence that Na(+),K(+)-ATPase can be regulated through tyrosine phosphorylation of primarily their alpha(1)-subunits, using PTP inhibitors.
...
PMID:Regulation of human and pig renal Na(+),K (+)-ATPase activity by tyrosine phosphorylation of their alpha(1)-subunits. 2013 Aug 47

Endosomal sorting complexes required for transport (ESCRTs) regulate several events involving membrane invagination, including multivesicular body (MVB) biogenesis, viral budding, and cytokinesis. In each case, upstream ESCRTs combine with additional factors, such as Bro1 proteins, to recruit ESCRT-III and the ATPase VPS4 in order to drive membrane scission. A clue to understanding how such diverse cellular processes might be controlled independently of each other has been the identification of ESCRT isoforms. Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B. These could generate several ESCRT-I complexes, each targeted to a different compartment and able to recruit distinct ESCRT-III proteins. Here we identify a novel ESCRT-I component, ubiquitin-associated protein 1 (UBAP1), which contains a region conserved in MVB12. UBAP1 binds the endosomal Bro1 protein His domain protein tyrosine phosphatase (HDPTP), but not Alix, a Bro1 protein involved in cytokinesis. UBAP1 is required for sorting EGFR to the MVB and for endosomal ubiquitin homeostasis, but not for cytokinesis. UBAP1 is part of a complex that contains a fraction of total cellular TSG101 and that also contains VPS37A but not VPS37C. Hence, the presence of UBAP1, in combination with VPS37A, defines an endosome-specific ESCRT-I complex.
...
PMID:UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting. 2240 94

Mycobacterium tuberculosis (Mtb) pathogenicity depends on its ability to inhibit phagosome acidification and maturation processes after engulfment by macrophages. Here, we show that the secreted Mtb protein tyrosine phosphatase (PtpA) binds to subunit H of the macrophage vacuolar-H(+)-ATPase (V-ATPase) machinery, a multisubunit protein complex in the phagosome membrane that drives luminal acidification. Furthermore, we show that the macrophage class C vacuolar protein sorting complex, a key regulator of endosomal membrane fusion, associates with V-ATPase in phagosome maturation, suggesting a unique role for V-ATPase in coordinating phagosome-lysosome fusion. PtpA interaction with host V-ATPase is required for the previously reported dephosphorylation of VPS33B and subsequent exclusion of V-ATPase from the phagosome during Mtb infection. These findings show that inhibition of phagosome acidification in the mycobacterial phagosome is directly attributed to PtpA, a key protein needed for Mtb survival and pathogenicity within host macrophages.
...
PMID:Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. 2208 3

The goal of the current work is to study the molecular mechanisms underlay the action of 5- amino-exo-3-azatricyclo[5.2.1.0(2,6)]decan-4-one (P-11) with combined antiarrhythmic, nootropic, anti-inflammatory and anaesthetic activities. The aconitine-induced experimental rat model of cardiac arrhythmia has been used in our study. Aconitine was administered once intravenously in a dose 50 microg/kg whereas experimental animal group received P-11 in a dose 0.3 mg/kg (the compound was injected intravenously 2 min before acute aconitine treatment). Expression macroarray (Atlas Rat cDNA Expression Array, #7738-1; BD Biosciences) was used to identify the target genes for P-11 compound. Comparative analysis of changes in the status of expression of genes in the heart of rats induced by P-11 against the simulated in vivo arrhythmia identified 16 genes that reproducibly alter the level of expression.These genes encode the extracellular matrix proteins (glypican 1, Gpc1; tissue inhibitor of metalloproteinase 2, 3, Timp2, Timp 3); intracellular signaling molecules (rho GTPase activating protein 7, Dlc1; protein tyrosine phosphatase 4a1, Ptp4a1; phosphodiesterase 4D, PDE4D; PI3-kinase regulatory subunit alpha, PIK3R1; guanine nucleotide binding protein alpha 12, Gna12) and protein of intermediate junctions (junction plakoglobin, Jup), proteins involved in glycolysis (phosphofructokinase I, Pfk1) and hemostasis (tissue plasminogen activator, Plat), plasma membrane transporters (Solute carrier family 16, member 1, Slc16a1; ATPase, Na+/K+ transporting, Atp1a), and ets. (c-fos protooncogene, c-fos; telomerase protein component 1, tlp; Annexin 1, anxa 1). Thus, the data about the selective effect of P-11 on genes whose products are involved in the aritmogenesys mechanisms, allow us to consider this compound as a promising means of pathogenetically oriented pharmacotherapy of cardiac arrhythmias.
...
PMID:[Animal in vivo model of arrhythmia for genes target identification for 5-amino-exo-3-azatricyclo[5.2.1.0(2,6)]decan-4-one]. 2249 81

Regucalcin was first identified in 1978 as a regulatory protein of Ca²⁺ signaling in liver cells. Regucalcin was shown to play a multifunctional role in cell regulation, such as maintainance of intracellular Ca²⁺ homeostasis and suppression of signal transduction, protein synthesis, nuclear function, cell proliferation and apoptosis in various types of cells and tissues. Cardiac excitation-contraction coupling is based on the regulation of intracellular Ca²⁺ concentration by the Ca²⁺ pump in the sarcoplasmic reticulum of heart muscle cells. Regucalcin, which is expressed in the heart, was found to increase rat heart sarcoplasmic reticulum Ca²⁺-ATPase activity and ATP-dependent Ca²⁺ uptake and mitochondrial Ca²⁺-ATPase activity. Regucalcin was also shown to suppress Ca²⁺-dependent protein tyrosine phosphatase, Ca²⁺/calmodulin-dependent protein phosphatase (calcineurin) and nitric oxide (NO) synthase activity in the heart cytoplasm. Moreover, regucalcin was found to activate superoxide dismutase (SOD), which plays a significant role in the prevention of cell death and apoptosis in the heart. Regucalcin may be a key molecule in heart muscle cell regulation through Ca²⁺ signaling. Regucalcin may also play a pathophysiological role in heart failure. The aim of this study was to review the recent findings regarding the role of regucalcin in Ca²⁺ signaling in the heart.
...
PMID:Regulatory role of regucalcin in heart calcium signaling: Insight into cardiac failure (Review). 2474 64

Noonan syndrome with multiple lentigines (NSML) is primarily caused by mutations in the nonreceptor protein tyrosine phosphatase SHP2 and associated with congenital heart disease in the form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Our goal was to elucidate the cellular mechanisms underlying the development of HCM caused by the Q510E mutation in SHP2. NSML patients carrying this mutation suffer from a particularly severe form of HCM. Drawing parallels to other, more common forms of HCM, we hypothesized that altered Ca(2+) homeostasis and/or sarcomeric mechanical properties play key roles in the pathomechanism. We used transgenic mice with cardiomyocyte-specific expression of Q510E-SHP2 starting before birth. Mice develop neonatal onset HCM with increased ejection fraction and fractional shortening at 4-6 wk of age. To assess Ca(2+) handling, isolated cardiomyocytes were loaded with fluo-4. Q510E-SHP2 expression increased Ca(2+) transient amplitudes during excitation-contraction coupling and increased sarcoplasmic reticulum Ca(2+) content concurrent with increased expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase. In skinned cardiomyocyte preparations from Q510E-SHP2 mice, force-velocity relationships and power-load curves were shifted upward. The peak power-generating capacity was increased approximately twofold. Transmission electron microscopy revealed that the relative intracellular area occupied by sarcomeres was increased in Q510E-SHP2 cardiomyocytes. Triton X-100-based myofiber purification showed that Q510E-SHP2 increased the amount of sarcomeric proteins assembled into myofibers. In summary, Q510E-SHP2 expression leads to enhanced contractile performance early in disease progression by augmenting intracellular Ca(2+) cycling and increasing the number of power-generating sarcomeres. This gives important new insights into the cellular pathomechanisms of Q510E-SHP2-associated HCM.
...
PMID:Elevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines. 2572 91

The Type 1 Diabetes Genetics Consortium (T1DGC) comprised groups of investigators from many countries throughout the world, with a common goal of identifying genes predisposing to type 1 diabetes. The T1DGC ascertained and collected samples from families with two or more affected siblings with type 1 diabetes and generated a broad array of clinical, genetic, and immunologic data. The T1DGC Autoantibody Workshop was designed to distribute data for analyses to discover genes associated with autoantibodies in those with type 1 diabetes. In the T1DGC-affected sibling pair families, three T1DGC Network laboratories measured antibodies to the islet autoantigens GAD65 and the intracellular portion of protein tyrosine phosphatase (IA-2A). The availability of extensive genetic data provided an opportunity to investigate the associations between type 1 diabetes and other autoimmune diseases for which autoantibodies could be measured. Measurements of additional nonislet autoantibodies, including thyroid peroxidase, tissue transglutaminase, 21-hydroxylase, and the potassium/hydrogen ion transporter H+/K+-ATPase, were performed by the T1DGC laboratory at the Barbara Davis Center for Childhood Diabetes, Aurora, CO. Measurements of all autoantibodies were transmitted to the T1DGC Coordinating Center, and the data were made available to members of the T1DGC Autoantibody Working Groups for analysis in conjunction with existing T1DGC genetic data. This article describes the design of the T1DGC Autoantibody Workshop and the quality-control procedures to maintain and monitor the performance of each laboratory and provides the quality-control results for the nonislet autoantibody measurements.
...
PMID:Design and Measurement of Nonislet-Specific Autoantibodies for the Type 1 Diabetes Genetics Consortium Autoantibody Workshop. 2640 71

It is well established that binding of p120 catenin to the cytoplasmic domain of surface cadherin prevents cadherin endocytosis and degradation, contributing to cell-cell adhesion. In the present work we show that p120 catenin bound to the N-cadherin precursor, contributes to its anterograde movement from the endoplasmic reticulum (ER) to the Golgi complex. In HeLa cells, depletion of p120 expression, or blocking its binding to N-cadherin, increased the accumulation of the precursor in the ER, while it decreased the localization of mature N-cadherin at intercellular junctions. Reconstitution experiments in p120-deficient SW48 cells with all three major isoforms of p120 (1, 3 and 4) had similar capacity to promote the processing of the N-cadherin precursor to the mature form, and its localization at cell-cell junctions. P120 catenin and protein tyrosine phosphatase PTP1B facilitated the recruitment of the N-ethylmaleimide sensitive factor (NSF), an ATPase involved in vesicular trafficking, to the N-cadherin precursor complex. Dominant negative NSF E329Q impaired N-cadherin trafficking, maturation and localization at cell-cell junctions. Our results uncover a new role for p120 catenin bound to the N-cadherin precursor ensuring its trafficking through the biosynthetic pathway towards the cell surface.
...
PMID:P120-Catenin Regulates Early Trafficking Stages of the N-Cadherin Precursor Complex. 2725 16

Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
...
PMID:Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency. 2840 71


<< Previous 1 2 3 Next >>

---