Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P67775 (alpha isoform)
 797 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Na,K-ATPase molecules containing the alpha 1, alpha 2*, and alpha 3* isoforms expressed in HeLa cells exhibit a two- to threefold difference in their K0.5 for Na+ (alpha 1 = alpha 2* < alpha 3*). To investigate the structural basis for this difference, chimeric alpha 1/alpha 3* isoform cDNAs were constructed and expressed in HeLa cells. Na,K-ATPase containing each alpha isoform chimera was analyzed for its Na+ dependence properties. Results of these experiments do not reveal a region in the alpha 1 or alpha 3* isoform that is clearly responsible for the apparent affinity for Na+. It is possible that molecular interactions involving amino acids that span virtually the entire Na,K-ATPase molecule contribute to the determination of this parameter.
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PMID:Chimeric rat Na,K-ATPase alpha 1/alpha 3* isoforms. Analysis of the structural basis for differences in Na+ requirements in the alpha 1 and alpha 3* isoforms. 128 13

The Na+,K(+)-ATPase alpha 3 isoform has recently been demonstrated immunochemically in human brain. Conclusive biochemical evidence, however, is still lacking. In this study, a unique 50-kDa polypeptide, which is known to be specific to the rat alpha 3 isoform, has been found in human brainstem Na+,K(+)-ATPase following formic acid treatment of the purified alpha isoform proteins. Human alpha 3 Na+,K(+)-ATPase is also highly sensitive to ouabain inhibition, with a 50% ouabain inhibition value of 1.0 x 10(-7) M. These results provide clear and direct evidence for the existence of the alpha 3 isoform in human brain.
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PMID:Highly ouabain-sensitive alpha 3 isoform of Na+,K(+)-ATPase in human brain. 131 Jul 23

The alpha isoform of phosphatidylinositol-specific phospholipase C (alpha-PI-PLC, Mr 62,000) was purified from bovine brain. Enzyme activity was dependent on calcium, sodium cholate and showed the anticipated specificity for the phosphatidylinositols. Calcium interaction with this protein, investigated by gel filtration chromatography, showed no detectable binding at calcium concentrations adequate to activate the enzyme. Association of alpha-PI-PLC with phospholipid vesicles was studied by light scattering, fluorescence energy transfer and gel-filtration chromatography. The enzyme readily associated with vesicles of high charge density, with vesicles of crude acidic phospholipids and with PIP2. Interaction was characterized by a rapid association followed by slower addition of more protein to the phospholipid. Complexes containing 20-30 percent protein (by weight) were readily obtained. Calcium had only a small effect on this interaction. The protein-phospholipid complexes appeared to bind less calcium than a similar amount of phospholipid alone. Thus, alpha-PI-PLC did not appear to be a calcium-binding protein in either its free or membrane-associated states. Although alpha-PI-PLC showed the highest propensity to bind to phospholipids, a number of other proteins also associated with phospholipids under the conditions used. Thus, whether or not the observed interaction of alpha-PI-PLC with membranes was specific and biologically important or whether it was a process common to many proteins, was not known. Knowledge of this interaction may enhance our understanding of possible mechanisms for protein-membrane interactions in general.
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PMID:Association of alpha-phosphatidylinositol-specific phospholipase C with phospholipid vesicles. 131

To investigate the functional role of the different Na+, K(+)-ATPase alpha (catalytic) subunit isoforms in neuronal cells, we used quantitative in situ hybridization with riboprobes specific for alpha 1, alpha 2, and alpha 3 isoforms to measure the level of alpha isoform-specific expression in the neuroendocrine cells of the supraoptic (SON) and paraventricular (PVN) nuclei of rat hypothalamus. A prolonged increase in electrical activity of these cells, achieved by 5 days of salt treatment, increased the amount of alpha 1 isoform mRNA in the SON and PVN by 50%. Levels of alpha 1 mRNA in other brain regions and levels of alpha 2 and alpha 3 mRNAs were not affected by salt treatment. We conclude that the alpha 1 isoform Na+, K(+)-ATPase may be specifically adapted to pump out Na+, which enters the cells through voltage-gated channels during neuronal depolarization.
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PMID:Activity-dependent regulation of Na+, K(+)-ATPase alpha isoform mRNA expression in vivo. 132 Dec 32

In photoreceptors, Na+, K(+)-ATPase maintains the ion gradients which power the dark current that sustains the response to light. The enzyme is composed of at least two polypeptides: alpha (the catalytic subunit) and beta. Three different isoforms of the alpha subunit and two isoforms of the beta subunit have been identified in rat. In some tissues, the isoenzymes have been shown to be differentially expressed during development or in response to varying physiological conditions. RNAs prepared from isolated photoreceptors and from whole retina were analyzed on blots that were hybridized with cDNA probes for the alpha 1, alpha 2, alpha 3, beta 1 and beta 2 isoforms. The predominant alpha and beta subunit mRNAs present in the photoreceptor preparation were those encoding the alpha 3 and beta 2 isoforms, accounting for 85% of the total alpha signal and 79% of the total beta signal, respectively. Proportions of each mRNA were similar in retina, but very different from those observed in two control tissues, brain and kidney. To confirm that the alpha-subunit mRNA species detected were translated, membranes prepared from isolated photoreceptors and whole retina were examined by immunoblotting. The antibodies detected a pattern of alpha isoform distribution in these tissues and in kidney and brain controls that agreed remarkably well with the pattern of mRNA expression in the same tissues. Moreover, the alpha 3 isoform was detectable in the inner segment plasma membrane of the photoreceptor by electron microscopic immunocytochemistry. These results indicate that alpha 3, and beta 2 are the predominant isoforms of Na+, K(+)-ATPase expressed in photoreceptors and retina.
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PMID:Na+, K(+)-ATPase of the photoreceptor: selective expression of alpha 3 and beta 2 isoforms. 217 74

Sodium, potassium-adenosine triphosphatase (Na+, K+-ATPase) is hypothesized to be involved in systemic vascular hypertension through its effects on smooth muscle reactivity and myocardial contractility. By means of RNA blot analyses of cardiac, aortic, and skeletal muscle RNAs in two rat hypertensive models, Na+,K+-ATPase alpha-subunit messenger RNA isoforms (alpha 2 and alpha 3) were shown to be deinduced in response to increased intravascular pressure. The changes were observed after 48 hours or more of experimental hypertension. Under these conditions, there is coordinate induction of another alpha isoform (alpha 1) and of beta-subunit messenger RNAs, probably in response to alterations in sodium flux rather than to elevated blood pressure.
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PMID:Isoform-specific modulation of Na+, K+-ATPase alpha-subunit gene expression in hypertension. 283 7

Prednisolone-3,20-bisguanylhydrazone (PBGH), a steroid derivative, has been shown to inhibit Na+,K+-ATPase isolated from guinea-pig heart or kidney in concentrations significantly lower than those required to inhibit the enzyme obtained from other sources. Because Na+,K+-ATPases obtained from guinea-pig heart or kidney are predominantly of the alpha isoform, the hypothesis that PBGH selectively inhibits the alpha isoform over alpha (+) isoform of the enzyme was tested. Sodium dodecylsulfate polyacrylamide gel electrophoresis of the enzyme preparations revealed the presence of only the higher mobility, alpha isoform in guinea-pig heart and ferret kidney, whereas those from guinea-pig brain, dog brain and ferret heart showed both high and low mobility isoforms corresponding to alpha and alpha (+) isoforms. Na+,K+-ATPase obtained from the guinea-pig heart was most sensitive to PBGH and those isolated from ferret heart or ferret kidney had the lowest sensitivity. Enzyme preparations obtained from dog brain, dog heart or guinea-pig brain had intermediate sensitivity. This spectrum of enzyme sensitivity to PBGH was markedly different from that to ouabain. In ferret heart Na+,K+-ATPase, a low concentration of PBGH preferentially inhibited [3H]ouabain binding to the high affinity ouabain binding sites (alpha(+) isoform). These results indicate that PBGH is not a specific inhibitor of the alpha isoforms of Na+,K+-ATPase. Affinity of the enzyme for PBGH is determined by the species and tissue rather than isoforms of Na+,K+-ATPase.
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PMID:Cardiac Na+,K+-ATPase isoenzymes: sensitivity to prednisolone bisguanylhydrazone. 285 75

Rat brain and kidney cDNA libraries were constructed and screened with a cDNA insert corresponding to the mRNA for the sheep kidney Na+,K+-ATPase catalytic subunit. The alpha-subunit cDNAs isolated from the kidney library were derived from a single class of messenger RNA, and the brain cDNAs were derived from three classes of messenger RNA. The most abundant brain cDNA, which spans 5.1 kilobases, encodes the alpha(+) form of the enzyme. The second most abundant brain cDNA, which spans 3.65 kilobases, is identical with that of the kidney form and therefore encodes the alpha isoform. The third class of cDNA, which spans 3.55 kilobases, was present at low abundance and encodes an isoform of the alpha-subunit, designated alpha III, which has not been identified previously. The complete nucleotide sequence and deduced amino acid sequence for each of the brain and kidney cDNAs have been determined. In addition, we have identified a lysine-rich sequence that may function as a movable, ion-selective gate during cation binding and occlusion and have also identified several amino acid sequence variations that appear to explain some of the well-known species and tissue differences in cardiac glycoside sensitivity.
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PMID:Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain. 302 70

The coexpression of multiple isoforms of the alpha and beta subunits of the Na,K-ATPase in mammalian tissues gives rise to the complex molecular heterogeneity that characterizes the Na pump. The expression of the different Na,K-ATPase isoforms in insect cells using recombinant baculoviruses represents a useful system for the analysis of Na,K-ATPase isoform function. In the present study, we use this system to direct the expression of the rat Na,K-ATPase alpha 3 beta 1 and alpha 3 beta 2 in sf-9 cells, a cell line derived from the ovary of the fall armyworm, Spodoptera frugiperda. The association of alpha 3 with either beta 1 or beta 2 results in catalytically competent Na,K-ATPase isozymes. Analysis of the kinetic characteristics of these enzymes demonstrates that the accompanying beta subunit isoform does not drastically affect the properties of the alpha 3 polypeptide. This is evidenced by the similar turnover numbers, apparent affinities for K+ and ATP, and the comparable high sensitivity to ouabain exhibited by both isozymes. The kinetic dependence on Na+, however, is different for both isozymes, with alpha 3 beta 2 displaying a 1.6-fold higher apparent affinity for the cation than alpha 3 beta 1. Comparison with other Na,K-ATPase isozymes shows that the apparent Na+ affinity of alpha 3 beta 2 is similar to that of the alpha 1 beta 1 Na pump widely expressed in every tissue; nevertheless, its reactivity toward K+, ATP, and ouabain are characteristic of the alpha 3 isoform. The most pronounced kinetic differences in Na,K-ATPase function are a result of variations in alpha isoform composition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the enzymatic properties of the Na,K-ATPase alpha 3 beta 1 and alpha 3 beta 2 isozymes. 763 89

The Na+,K(+)-ATPase alpha subunit has three known isoforms, alpha 1, alpha 2 and alpha 3, each encoded by a separate gene. This study was undertaken to determine the functional status of a fourth human alpha-like gene, ATP1AL2. Partial genomic sequence analysis revealed regions exhibiting sequence similarity with exons 3-6 of the Na+,K(+)-ATPase alpha isoform genes. ATP1AL2 cDNAs spanning the coding sequence of a novel P-type ATPase alpha subunit were isolated from a rat testis library. The predicted polypeptide is 1028 amino acids long and exhibits 76-78% identity with the rat Na+,K(+)-ATPase alpha 1, alpha 2 and alpha 3 isoforms, indicating that ATP1AL2 may encode a fourth Na+,K(+)-ATPase alpha isoform. A 3.9-kb mRNA is expressed abundantly in human and rat testis.
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PMID:A putative fourth Na+,K(+)-ATPase alpha-subunit gene is expressed in testis. 780 53


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