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)

Na+,K(+)-ATPase in renal epithelial cells plays an important role in the regulation of Na+ balance, extracellular volume and blood pressure. The function of renal Na+,K(+)-ATPase in Dahl salt-sensitive (DS) rats, an animal model for salt-sensitive hypertension, and Dahl salt-resistant (DR) rats has been studied. In Na+,K(+)-ATPase partially purified from renal cortex, affinities and the Hill coefficients for Na+ and K+ activation were similar in DS and DR rats. Only one component of low ouabain affinity site was found in both strains, indicating the presence of the alpha 1 isoform. Protein kinase C and cAMP-dependent protein kinase phosphorylated Na+,K(+)-ATPase alpha subunit in DS and DR rats, and the phosphorylation by protein kinase C was associated with an inhibition of enzyme activity. The kinetic parameters for K+ activation were also studied in a preparation of basolateral membranes and were found to be similar in DS and DR rats. In a preparation of cortical tubule cells, Na+,K(+)-ATPase activity was determined as ouabain-sensitive oxygen consumption (OS QO2). Maximal OS QO2, measured in Na+ loaded cells, was the same in DS and DR rats. The K0.5 for K+ was significantly lower in DS than DR rats (0.163 +/- 0.042 vs. 0.447 +/- 0.061 mM, P < 0.05), indicating that factors regulating Na+,K(+)-ATPase activity in intact cells are altered in DS rats. Kinetic parameters for Na+ activation in cells were the same in both strains. In summary, the function of renal Na+,K(+)-ATPase molecule is not altered in DS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal Na+,K(+)-ATPase in Dahl salt-sensitive rats: K+ dependence, effect of cell environment and protein kinases. 831 Aug 42

Kinesin is an ubiquitous heterotetrameric microtubule-based motor which translocates membrane-bound organelles. Since organelle motility and motor protein function can be regulated by components of signaling pathways, the ability of purified bovine brain kinesin (kinesin) to be phosphorylated and to recognize calmodulin (CaM) was tested. Extensively purified "kinesin" was found to consist of several forms of both heavy (KHC) and light (KLC) chains. Phosphorylation of kinesin by a variety of protein kinases was examined; cAMP-dependent protein kinase (cAMP-PK) was the most active enzyme leading to the incorporation of up to 8 mol P/mol kinesin. Phosphorylation occurred predominantly on the KLCs and led to substantial acidic pI shifts. Peptide maps indicated that multiple phosphorylation sites exist on each KLC. Incubation of kinesin in vitro with protein kinase C (PKC) led to the phosphorylation of both KHCs and KLCs. In vivo phosphorylation of KHC and KLCs was demonstrated by immunoprecipitation of [32P]-labeled kinesin from cultured rat hippocampal pyramidal neurons; kinesin phosphorylation was stimulated by 8-chlorophenyl-thio-cAMP or 12-O-tetradecanoylphorbol-13-acetate. Native bovine brain kinesin was shown to bind 125I-CaM by nucleotide-dependent pelleting with stable microtubules. Specific calcium-dependent binding of 125I-CaM to KLCs but not KHC was found using a ligand blotting assay. cAMP-PK phosphorylated kinesin bound 125I-CaM less well than untreated protein in both ligand blotting and microtubule-pelleting paradigms. Calcium-dependent binding of CaM to kinesin inhibited the ATPase activity of native kinesin but not of cAMP-PK phosphorylated kinesin. These results suggest that the KLCs have a regulatory function and integrate information coming from diverse signaling pathways to modulate the activity and function of kinesin.
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PMID:Calmodulin binding to and cAMP-dependent phosphorylation of kinesin light chains modulate kinesin ATPase activity. 838 85

The heat shock response is an inducible protective system of all living cells. It simultaneously induces both heat shock proteins and an increased capacity for the cell to withstand potentially lethal temperatures (an increased thermotolerance). This has lead to the suspicion that these two phenomena must be inexorably linked. However, analysis of heat shock protein function in Saccharomyces cerevisiae by molecular genetic techniques has revealed only a minority of the heat shock proteins of this organism having appreciable influences on thermotolerance. Instead, physiological perturbations and the accumulation of trehalose with heat stress may be more important in the development of thermotolerance during a preconditioning heat shock. Vegetative S. cerevisiae also acquires thermotolerance through osmotic dehydration, through treatment with certain chemical agents and when, due to nutrient limitation, it arrests growth in the G1 phase of the cell cycle. There is evidence for the activities of the cAMP-dependent protein kinase and plasma membrane ATPase being very important in thermotolerance determination. Also, intracellular water activity and trehalose probably exert a strong influence over thermotolerance through their effects on stabilisation of membranes and intracellular assemblies. Future investigations should address the unresolved issue of whether the different routes to thermotolerance induction cause a common change to the physical state of the intracellular environment, a change that may result in an increased stabilisation of cellular structures through more stable hydrogen bonding and hydrophobic interactions.
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PMID:Molecular events associated with acquisition of heat tolerance by the yeast Saccharomyces cerevisiae. 839 11

A functional approach was utilized to isolate protein effectors from cAMP-stimulated rabbit gastric microsomes capable of stimulating H(+)-K(+)-ATPase activity. These studies have resulted in isolation of a cAMP-dependent protein kinase product from rabbit gastric microsomes which is capable of stimulating the proton pump of the parietal cell, H(+)-K(+)-ATPase, in inhibited gastric microsomes. This protein is membrane-bound and may be extracted from gastric microsomes only in the phosphorylated state. This phosphoprotein has at least 20 phosphorylation sites and produces enhancement of H(+)-K(+)-ATPase activity which equals that induced by the K+ ionophore, valinomycin. It would appear, therefore, that cAMP-mediated acid secretion involves phosphorylation of a membrane-bound cAMP-dependent protein kinase substrate in close proximity to the proton pump which produces K+ conductance and thereby controls the rate of acid secretion. The degree of phosphorylation of this protein is probably controlled by the activities of cAMP-dependent protein kinase and phosphoprotein phosphatase.
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PMID:Regulation of gastric H(+)-K(+)-ATPase by cAMP-dependent protein kinase. 841 3

The cAMP-dependent protein kinase is a bifunctional enzyme, catalyzing the phosphorylation of the serine and threonine residues in peptides and proteins (kinase activity) as well as the phosphorylation of water (ATPase activity). We have found that several peptides, which serve as inhibitors of the kinase reaction, will either maintain or enhance the ATPase reaction catalyzed by the enzyme. Positively charged dipeptides (e.g. Arg-Arg), as well as small guanidino-containing compounds (e.g. guanethidine) block protein kinase activity yet enhance ATPase activity up to 3.5-fold over that exhibited by the enzyme in the absence of these compounds. In contrast, several nonphosphorylatable peptides, whose primary sequences are based on that of a known substrate (i.e. Leu-Arg-Arg-Ala-Ser-Leu-Gly), such as Leu-Arg-Arg-Ala-Ala-Leu-Gly, Leu-Arg-Arg-Ala-Phe-Leu-Gly, and Leu-Arg-Arg-Ala-Tyr-Leu-Gly, have little or no effect on the rate of the kinase-catalyzed hydrolysis of ATP. An exception to the latter observation is Leu-Arg-Arg-Ala-Cys-Leu-Gly, a cysteine-containing peptide that promotes the protein kinase-catalyzed ATPase reaction by 2.2-fold. We have also found that peptides that possess relatively large amino acid side chain moieties immediately following the arginine dyad (i.e. such as Phe, Tyr, Cys, or Asn at Xaa in Leu-Arg-Arg-Xaa-Ala-Leu-Gly) sharply reduce the rate of enzyme-catalyzed ATP hydrolysis. This suggests that in the presence of peptides containing an -Arg-Arg-Ala- sequence, the enzyme-bound gamma-phosphate of ATP is relatively accessible to water. In contrast, when the latter alanine moiety is replaced by a larger residue, access by water to ATP appears to be hindered. These results indicate that certain structural features associated with the substrate or substrate analog have a profound influence on the manner by which these species interact with the protein kinase. Furthermore, the work described herein demonstrates that it is possible to block the physiologically important kinase reaction and simultaneously promote the energetically wasteful ATPase reaction.
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PMID:ATPase-promoting dead end inhibitors of the cAMP-dependent protein kinase. 850 66

Characterization of two mitochondrial proteins of M(r) 42 and 18 kDa, respectively, phosphorylated by the cAMP-dependent protein kinase of bovine heart mitochondria (mtPKA), is presented. A 42 kDa protein is found to be loosely associated to complexes I, III and IV of the respiratory chain and complex V (ATP synthase) in the inner mitochondrial membrane. An 18 kDa protein is associated to complex I in the inner membrane and in a purified preparation of this complex where it can be phosphorylated by the isolated catalytic subunit of PKA.
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PMID:Characterization of proteins phosphorylated by the cAMP-dependent protein kinase of bovine heart mitochondria. 854 78

Maintenance of cytoplasmic pH (pHi) within a narrow physiological range is crucial to normal cellular function. This is of particular relevance to phagocytic cells within the acidic inflammatory microenvironment where the pHi tends to be acid loaded. We have previously reported that a vacuolar-type H(+)-ATPase (V-ATPase) situated in the plasma membrane of macrophages and poised to extrude protons from the cytoplasmic to the extracellular space is an important pHi regulatory mechanism within the inflammatory milieu. Since this microenvironment is frequently characterized by the influx of cells known to release inflammatory cytokines, we performed studies to examine the effect of one such mediator molecule, interleukin-1 (IL-1), on pHi regulation in peritoneal macrophages. IL-1 caused a time- and dose-dependent increase in macrophage pHi recovery from an acute acid load. This effect was specific to IL-1 and was due to enhanced plasmalemmal V-ATPase activity. The increased V-ATPase activity by IL-1 occurred following a lag period of several hours and required de novo protein and mRNA synthesis. However, Northern blot analysis revealed that IL-1 did not exert its effect via alterations in the levels of mRNA transcripts for the A or B subunits of the V-ATPase complex. Finally, stimulation of both cAMP-dependent protein kinase and protein kinase C was required for the stimulatory effect of IL-1 on V-ATPase activity. Thus, cytokines present within the inflammatory milieu are able to modulate pHi regulatory mechanisms. These data may represent a novel mechanism whereby cytokines may improve cellular function at inflammatory sites.
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PMID:Interleukin-1 increases vacuolar-type H+-ATPase activity in murine peritoneal macrophages. 856 51

Regulation of calcium transport by sarcoplasmic reticulum provides increased cardiac contractility in response to beta-adrenergic stimulation. This is due to phosphorylation of phospholamban by cAMP-dependent protein kinase or by calcium/calmodulin-dependent protein kinase, which activates the calcium pump (Ca2+-ATPase). Recently, direct phosphorylation of Ca2+-ATPase by calcium/calmodulin-dependent protein kinase has been proposed to provide additional regulation. To investigate these effects in detail, we have purified Ca2+-ATPase from cardiac sarcoplasmic reticulum using affinity chromatography and reconstituted it with purified, recombinant phospholamban. The resulting proteoliposomes had high rates of calcium transport, which was tightly coupled to ATP hydrolysis (approximately 1.7 calcium ions transported per ATP molecule hydrolyzed). Co-reconstitution with phospholamban suppressed both calcium uptake and ATPase activities by approximately 50%, and this suppression was fully relieved by a phospholamban monoclonal antibody or by phosphorylation either with cAMP-dependent protein kinase or with calcium/calmodulin-dependent protein kinase. These effects were consistent with a change in the apparent calcium affinity of Ca2+-ATPase and not with a change in Vmax. Neither the purified, reconstituted cardiac Ca2+-ATPase nor the Ca2+-ATPase in longitudinal cardiac sarcoplasmic reticulum vesicles was a substrate for calcium/calmodulin-dependent protein kinase, and accordingly, we found no effect of calcium/calmodulin-dependent protein kinase phosphorylation on Vmax for calcium transport.
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PMID:Purified, reconstituted cardiac Ca2+-ATPase is regulated by phospholamban but not by direct phosphorylation with Ca2+/calmodulin-dependent protein kinase. 866 79

Ca2+ transport by cardiac sarcoplasmic reticulum is tightly coupled with the enzymatic activity of Ca2+-dependent ATPase, which forms and decomposes an intermediate phosphoenzyme. Heart sarcoplasmic reticulum Ca2+ pump is regulated by cAMP-dependent protein kinase (PKA) phospholamban phosphorylation, which results in a stimulation of the initial rates of Ca2+ transport and Ca2+ ATPase activity. In the present studies we found that acylphosphatase from heart muscle, used at concentrations within the physiological range, actively hydrolyzes the phosphoenzyme of cardiac sarcoplasmic reticulum Ca2+ pump, with an apparent Km on the order of 10(-7) M, suggesting an high affinity of the enzyme for this special substrate. In unphosphorylated vesicles acylphosphatase enhanced the rate of ATP hydrolysis and Ca2+ uptake with a concomitant significant decrease in apparent Km for Ca2+ and ATP. In vesicles whose phospholamban was PKA-phosphorylated, acylphosphatase also stimulated the rate of Ca2+ uptake and ATP hydrolysis but to a lesser extent, and the Km values for Ca2+ and ATP were not significantly different with respect to those found in the absence of acylphosphatase. These findings suggest that acylphosphatase, owing to its hydrolytic effect, accelerates the turnover of the phosphoenzyme intermediate with the consequence of an enhanced activity of Ca2+ pump. It is known that phosphorylation of phospholamban results in an increase of the rate at which the phosphoenzyme is decomposed. Thus, as discussed, a competition between phospholamban and acylphosphatase effect on the phosphoenzyme might be proposed to explain why the stimulation induced by this enzyme is less marked in PKA-phosphorylated than in unphosphorylated heart vesicles.
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PMID:Stimulation of cardiac sarcoplasmic reticulum calcium pump by acylphosphatase. Relationship to phospholamban phosphorylation. 870 78

The effects of cyclic AMP (cAMP) on intracellular Na+ concentration ([Na+]i), membrane depolarization and intracellular Ca2+ concentration ([Ca2+]i) and the involvement of cAMP in acetylcholine (ACh)-induced such cellular events and catecholamine (CA) release were studied in cultured bovine adrenal medullary chromaffin cells. 8-Bromo-cyclic AMP (8Br-cAMP) and forskolin caused a rise in [Na+]i, membrane depolarization and a rise in [Ca2+]i and potentiated these responses and CA release to ACh. The effects of 8Br-cAMP or forskolin on ACh-induced changes of but not on basal level of [Na+]i, membrane potential and [Ca2+]i were blocked by tetrodotoxin (TTX, 1 microM). In Na+ deprivated medium, forskolin failed to produce an increase in basal [Ca2+]i level and to potentiate ACh-induced rise. The similar results as in 8Br-cAMP and forskolin were obtained using ouabain, and 8Br-cAMP or foskolin produced no further effects in the presence of ouabain. Inhibitors of cAMP-dependent protein kinase not only blocked the effects of 8Br-cAMP and forskolin on membrane depolarization, [Ca2+]i rise and CA release, but also reduced these responses to ACh. From the similarity between the effects of cAMP and those of ouabain on the cellular events and the counteraction of the effects of cAMP by ouabain, it may be suggested that cAMP produces its effects on ion fluxes and CA release probably via an inhibition of Na+, K(+)-ATPase in intact chromaffin and cAMP may participate in the responses to ACh.
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PMID:Cyclic AMP enhances acetylcholine (ACh)-induced ion fluxes and catecholamine release by inhibiting Na+, K(+)-ATPase and participates in the responses to ACh in cultured bovine adrenal medullary chromaffin cells. 874 60


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