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)

1. The contractile actions of vanadate (VO4) and pervanadate (PV, peroxide(s) of vanadate) were studied in rat gastric longitudinal muscle strips and in aortic rings. The roles of extracellular sodium and calcium were evaluated and the potential effects of nerve-released agonists were considered. The possibility that these responses were due to the potentiation of tyrosine kinase activity, as a result of PV-mediated tyrosine phosphatase inhibition was explored with the use of tyrosine kinase inhibitors (genistein, tyrphostin) and by Western blot analysis of phosphotyrosyl proteins in PV-treated tissues. The ability of PV to mimic the action of the tyrosine kinase receptor-associated agonist, epidermal growth factor-urogastrone (EGF-Uro), in the gastric preparation was also studied. 2. PV caused concentration-dependent contractions in both gastric and aorta-derived tissues, with a potency that was 1 to 2 orders of magnitude greater than that of VO4. 3. Although repeated exposure of gastric and aortic tissues to a fixed concentration of VO4 caused reproducible contractions in both tissues, repeated exposure of gastric tissue to PV caused an increased contractile response plateauing after 3 exposures. In contrast, a single exposure of aortic tissue to PV (20 microM) caused a prolonged desensitization of the tissue to the subsequent contractile actions of PV or other agonists. 4. The contractile responses to PV were unaffected in both preparations by tetrodotoxin, atropine, yohimbine and phenoxybenzamine; and in the aortic preparation, the responses to VO4 and PV were the same in the presence or absence of a functional endothelium. 5. PV-induced contractions in both tissues were observed in the absence of extracellular sodium but required extracellular calcium and were attenuated by 1 micro M nifedipine.6. In the gastric preparation, the characteristics of the contractile actions of PV paralleled those of EGF-Uro in terms of (1) inhibition by genistein, (2) inhibition by indomethacin and (3) a requirement for extracellular calcium. These response characteristics differed from those of other contractile agonists such as carbachol.7. In both the gastric and aortic preparations genistein was able to inhibit PV-induced contractions selectively without causing comparable inhibition of KCI-induced contractions. Tyrphostin (AG18) also selectively blocked PV-induced contractions in the gastric, but not in the aortic preparation.8. In both the gastric and aortic tissue, in step with an increased contractile response, PV caused increases in tissue phosphotyrosyl protein content, as detected by Western blot analysis using a monoclonal antiphosphotyrosine antibody; the increases in phosphotyrosyl protein content were reduced when tissues were treated with PV at the same time as a tyrosine kinase inhibitor.9 PV, at sub-contractile concentrations, potentiated the contractile action of angiotensin II in both the gastric and aorta tissue.10 We conclude that the growth factor-mimetic agent, PV, is a much more potent contractile agonist than V04 in both vascular and gastric smooth muscle tissue. PV can cause enhanced tissue phosphotyrosyl protein content most likely via the inhibition of tissue protein tyrosine phosphatases. The contractile actions of PV, which require extracelullar calcium and are independent of extracellular sodium, would appear not to be due either to Na+/Ca2" exchange, promoted by Na+/K+-ATPase inhibition or to the inhibition of Ca2+-ATPase and might be best explained by the ability of PV, via tyrosine phosphatase inhibition, to potentiate a tyrosine kinase pathway linked to calcium entry and to the contractile process.
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PMID:Regulation of vascular and gastric smooth muscle contractility by pervanadate. 753 May 69

Progesterone (P) has previously been shown to induce a rapid increase in [Ca2+]i as well as tyrosine phosphorylation of proteins in human spermatozoa. Both these effects are essential for induction of the acrosome reaction by P. We investigated a possible relationship between the P-induced calcium increase and tyrosine kinase activation, by evaluating the effect of the tyrosine kinase inhibitor genistein on these two effects. We found that preincubation with genistein abolished P-induced tyrosine phosphorylation of two sperm proteins of 97 and 75 kDa molecular weight and significantly inhibited the plateau phase of P-induced [Ca2+]i increase without affecting the peak phase. Conversely, the plateau phase was enhanced by the tyrosine phosphatase inhibitor Na3VO4. The effect of genistein was specific for P, since no inhibition was observed on the [Ca2+]i increase induced by thapsigargin, an inhibitor of endoplasmic Ca(2+)-ATPase previously shown to mobilize Ca2+ in spermatozoa. These results indicate that tyrosine kinase activation is involved in the generation of the plateau phase of Ca2+ influx induced by P, and suggest the possibility that two different pathways are involved in the induction of Ca2+ entry by P in human sperm.
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PMID:Tyrosine kinase inhibition reduces the plateau phase of the calcium increase in response to progesterone in human sperm. 775 May 49

The endomembrane Ca(2+)-ATPase inhibitor, thapsigargin, was used to deplete the intracellular Ca2+ stores of fura-2-loaded human platelets. In control cells, thapsigargin evoked a rise in cytosolic [Ca2+] and a substantial increase in protein tyrosine phosphorylation. Thapsigargin also evoked an increase in tyrosine phosphorylation in cells co-loaded with fura-2 and the Ca2+ chelator dimethyl BAPTA, such that the rise in cytosolic [Ca2+] was abolished. These data support the existence of a tyrosine phosphatase regulated by the Ca2+ content of the intracellular store, a requirement of the putative model for reciprocal control of Ca2+ entry by cytosolic and store [Ca2+] via protein tyrosine phosphorylation.
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PMID:Calcium store depletion in dimethyl BAPTA-loaded human platelets increases protein tyrosine phosphorylation in the absence of a rise in cytosolic calcium. 800 12

Phosphorylation of the alpha-subunit of Na+,K(+)-ATPase plays an important role in the regulation of this pump. Recent studies suggest that insulin, known to increase solute and fluid reabsorption in mammalian proximal convoluted tubule (PCT), is stimulating Na+,K(+)-ATPase activity through the tyrosine phosphorylation process. This study was therefore undertaken to evaluate the role of tyrosine phosphorylation of the Na+,K(+)-ATPase alpha-subunit in the action of insulin. In rat PCT, insulin and orthovanadate (a tyrosine phosphatase inhibitor) increased tyrosine phosphorylation level of the alpha-subunit more than twofold. Their effects were not additive, suggesting a common mechanism of action. Insulin-induced tyrosine phosphorylation was prevented by genistein, a tyrosine kinase inhibitor. The site of tyrosine phosphorylation was identified on Tyr-10 by controlled trypsinolysis in rat PCTs and by site-directed mutagenesis in opossum kidney cells transfected with rat alpha-subunit. The functional relevance of Tyr-10 phosphorylation was assessed by 1) the abolition of insulin-induced stimulation of the ouabain-sensitive (86)Rb uptake in opossum kidney cells expressing mutant rat alpha1-subunits wherein tyrosine was replaced by alanine or glutamine; and 2) the similarity of the time course and dose dependency of the insulin-induced increase in ouabain-sensitive (86)Rb uptake and tyrosine phosphorylation. These findings indicate that phosphorylation of the Na+,K(+)-ATPase alpha-subunit at Tyr-10 likely participates in the physiological control of sodium reabsorption in PCT.
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PMID:Insulin-induced stimulation of Na+,K(+)-ATPase activity in kidney proximal tubule cells depends on phosphorylation of the alpha-subunit at Tyr-10. 1047 31

To determine how angiotensin II inhibits the Na(+) pump (Na(+), K(+)-ATPase) in rat zona glomerulosa, we selectively blocked signaling proteins that could be activated by the angiotensin AT(1) receptor and known to affect Na(+) pump activity. Inhibitors of protein kinase C [calphostin C (1 microM); staurosporine (1 microM)], phospholipase A(2) [arachidonyl triflouromethyl ketone (25 microM); quinacrine (75 microM)], diacylgycerol lipase [RHC-80267 (5 microM)], and tyrosine phosphorylation [tyrphostin 47 (100 microM)] had no effect on angiotensin II inhibition of the Na(+) pump. On the other hand, inhibitors of tyrosine phosphatases [phenylarsine oxide (5 microM) and 4-bromotetramisole oxalate (100 microM)] blocked angiotensin II inhibition, where as inhibitors of serine/threonine phosphatases [okadaic acid (1 microM) and microcystin (1.5 microM)] did not. Thus, angiotensin II inhibition of the Na(+) pump may in part be mediated by a tyrosine phosphatase.
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PMID:Inhibitors of tyrosine phosphatases block angiotensin II inhibition of Na(+) pump. 1101 Oct 32

The hypothesis that protein kinase C (PKC) and tyrosine kinases, as well as serine-threonine and tyrosine phosphatases, are involved in prolactin (PRL) signalling in theca cells harvested from porcine follicles was tested. Theca cells were incubated with PRL for 24 h to stimulate progesterone (P4) production. In addition, treatments included inhibitors of PKC and tyrosine kinases, as well as serine-threonine phosphatase inhibitor and tyrosine phosphatase inhibitor. Prolactin significantly stimulated P4 production by theca cells and all inhibitors suppressed the PRL-stimulated P4 production. After incubation with PRL for 2, 5, 10 or 20 min, theca cells were homogenized and cytosolic and membrane fractions were obtained. This was followed by determination of PKC activity in partially purified subcellular fractions by measuring the transfer of 32P from [gamma-32P] adenosine triphosphatase (ATP) to histone III-S. In unstimulated porcine theca cells the major proportion of PKC activity was present in the cytosol. Incubation of cells with PRL resulted in a rapid, time-dependent increase in the amount of PKC activity in the membrane fraction. Protein kinase C activity in the membrane fraction was maximal after 10 min of cells' exposure to PRL. Protein kinase C activation was assessed also by measuring the specific association of 3H-phorbol dibutyrate (3H-PDBu) with theca cells after treatment with PRL. Prolactin significantly increased 3H-PDBu-specific binding in theca cells. In contrast to PKC, total inositol phosphate accumulation was not affected by PRL in the current study. In summary, PRL stimulated P4 production by porcine theca cells derived from large follicles. The results of the study were consistent with the hypothesis that PKC is one of the intracellular mediators of PRL action in porcine theca cells. Protein kinase C activation does not appear to occur through the action of phosphatidylinositol-dependent phospholipase C. Moreover, the involvement of tyrosine kinases, as well as tyrosine and serine-threonine phosphatases, in PRL signalling in the examined cells is suggested.
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PMID:Prolactin signalling in porcine theca cells: the involvement of protein kinases and phosphatases. 1272 1

Human neutrophil adherence to ECMs induces an initial inhibition of stimulated reactive oxygen species (ROS) formation, followed by an enhanced phase of oxidant production. The initial integrin-mediated suppression of ROS constitutes a mechanism to prevent inappropriate tissue damage as leukocytes migrate to inflammatory sites. The Rac2 guanosine 5'-triphosphatase (GTPase) is a critical regulatory component of the phagocyte NADPH oxidase. We show that activation of Rac2 is inhibited in adherent neutrophils, correlating with inhibition of ROS formation. Conversely, NADPH oxidase components p47 and p67 assemble normally, suggesting a specific action of adhesion on the Rac2 molecular switch. Reconstitution with activated Rac2 restored rapid NADPH oxidase activation kinetics to adherent neutrophils, establishing that inhibition was due to defective Rac2 activity. We provide evidence that integrins inhibit Rac2 activation via a membrane-associated guanine nucleotide exchange factor, likely to be Vav1. Activation of Vav1, but not its upstream activator, Syk, is suppressed by cell adhesion. Vav1 activity is inhibited due to dephosphorylation of the regulatory Tyr174 via enhanced tyrosine phosphatase activity in adherent cells. These studies identify an integrin-mediated pathway in which Vav1 is as a strong candidate for the critical regulatory point in suppression of Rac2 activation and ROS generation during inflammatory responses.
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PMID:The molecular basis for adhesion-mediated suppression of reactive oxygen species generation by human neutrophils. 1466 Jul 49

Human granulocytic anaplasmosis (HGA) is caused by the obligate intracellular bacterium Anaplasma phagocytophilum. The bacterium infects, survives, propagates in, and alters neutrophil phenotype, indicating unique survival mechanisms. AnkA is the only known A. phagocytophilum component that gains access beyond neutrophil vacuoles and is transported to the infected host cell nucleus. The ability of native and recombinant AnkA to bind DNA and nuclear proteins from host HL-60 cells was assessed by the use of immunoprecipitation after cis-diamminedichloroplatinum (cis-DDP) DNA-protein crosslinking, by probing uninfected HL-60 cell nuclear lysates for AnkA binding, and by recovery and sequence analysis of immunoprecipitated DNA. AnkA binds HL-60 cell DNA as well as nuclear proteins of approximately 86, 53 and 25 kDa, whereas recombinant A. phagocytophilum Msp2 or control proteins do not. DNA immunoprecipitation reveals AnkA binding to a variety of target genes in the human genome, including genes that encode proteins with ATPase, tyrosine phosphatase and NADH dehydrogenase-like functions. These data indicate that AnkA could exert some effect on cells through binding to protein:DNA complexes in neutrophil nuclei. Whether AnkA binding leads to neutrophil functional alterations, and how such alterations might occur will depend upon definitive identification of binding partners and associated metabolic and biochemical pathways.
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PMID:Anaplasma phagocytophilum AnkA binds to granulocyte DNA and nuclear proteins. 1523 41

Interaction of 14-3-3 proteins with their targets depends not only on the phosphorylation status of the target but also on that of 14-3-3 (Fu et al., 2000). In this work we demonstrated that the maize 14-3-3 isoform GF14-6 is a substrate of the tyrosine kinase insulin growth factor receptor 1. By means of site-directed mutants of GF14-6, we identified Tyr-137 as the specific tyrosine residue phosphorylated by the insulin growth factor receptor 1. Phosphorylation of GF14-6 on Tyr-137 lowered its affinity for a peptide mimicking the 14-3-3 binding site of the plant plasma membrane H+-ATPase. Moreover, phosphorylation in planta of 14-3-3 tyrosine residues, resulting from incubation with the tyrosine phosphatase inhibitor, phenylarsine oxide, decreased their association to the H+-ATPase.
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PMID:Tyrosine phosphorylation inhibits the interaction of 14-3-3 proteins with the plant plasma membrane H+-ATPase. 1524 25

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


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