Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Cys127-Cys150 disulfide-bonded loop (L1) of the Torpedo californica Na,K-ATPase beta 1 subunit was substituted with the corresponding loop of the rat beta 1, mouse beta 2, or pig H,K-ATPase beta subunit. All the substituted mutant beta subunits assembled with the Na,K-ATPase alpha subunit in a trypsin-resistant manner. The mutants with L1 from the Na,K-ATPase beta subunit isoforms (rat beta 1 and mouse beta 2) each formed a functional complex with the Na,K-ATPase alpha subunit. On the other hand, the complex of the alpha subunit with the mutant beta subunit that was substituted with the pig H,K-ATPase beta subunit L1 was inactive as to ATP hydrolysis. Ser131 and Phe148 located within L1 of the pig H,K-ATPase beta subunit-substituted mutant were back-mutated to Pro131 and Arg148, respectively. The Phe148 to Arg mutation restored the ability of the mutant beta subunit substituted with the H,K-ATPase beta subunit L1 to form a functional complex with the alpha subunit. These results suggested that the Cys127-Cys150 loop of the Na,K-ATPase beta 1 subunit, especially Arg148, plays a critical role in the functional expression of Na,K-ATPase.
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PMID:Functional consequences of substitution of the disulfide-bonded segment, Cys127-Cys150, located in the extracellular domain of the Na,K-ATPase beta subunit: Arg148 is essential for the functional expression of Na,K-ATPase. 762 27

Incubation of primary cultures of neonatal rat cardiac myocytes in the presence of 100 nM triiodothyronine (T3) resulted in a three- to fivefold increase in the content of Na,K-ATPase beta 1 subunit mRNA which was maximal at 1 d of exposure to hormone. To investigate the mechanism by which T3 stimulates the abundance of beta 1 mRNA, transient transfection experiments were conducted with a chimeric gene containing a portion of the 5' end of the rat beta 1 gene linked to a luciferase reporter gene. We found no effect of T3 on chimeric gene activity either in the absence or presence of cotransfected T3 receptor. The effect of T3 on the transcription rate of the endogenous beta 1 gene was quantitated by the nuclear run-on assay. T3 had no effect on beta 1 gene transcription following either 1 or 3 d of exposure and yielded a 1.3-fold increase at 6 d. These data indicate that T3 induction of Na,K-ATPase beta 1 mRNA content in neonatal rat cardiac myocytes in vitro is primarily mediated at a post-transcriptional site.
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PMID:Regulation of Na,K-ATPase beta 1 mRNA content by thyroid hormone in neonatal rat cardiac myocytes. 829 39

The human Na,K-ATPase beta 1 subunit gene promoter activity is stimulated by thyroid hormone (T3) in the human intestinal Caco-2 cells. To identify potential cis-acting transcriptional regulatory elements involved in this process, chimeric plasmids containing varying lengths of the 5' flanking region of the human beta 1 Na,K-ATPase gene linked to the firefly luciferase reporter gene were introduced into Caco-2 cells by transient transfection. Analysis of T3-regulated luciferase activity of cells carrying these plasmids, and subsequent use of site-directed mutagenesis revealed that a region from -459 to -438 (relative to the transcriptional start site) is required for the induction of the beta 1 Na,K-ATPase gene by T3. An oligonucleotide containing this sequence from -465 to -433 confers T3 responsiveness to a heterologous promoter. Gel mobility shift assays showed specific binding of nuclear proteins of Caco-2 cells to this region and immunoreactive T3 receptor was identified in one of these complexes. These data demonstrate that there is a cis-acting thyroid hormone responsive element in the 5' flanking region of the human beta 1 Na,K-ATPase gene and induction of transcription of this gene by T3 involves specific binding of the thyroid hormone receptor to the TRE located at position -459 to -438.
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PMID:Identification of a functional thyroid hormone response element in the upstream flanking region of the human Na,K-ATPase beta 1 gene. 839 3

Treatment of avian myelomonocytic cells with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) results in an approximately two fold increase in levels of Na,K-ATPase beta 1 subunit mRNA and protein (both total and plasma membrane-associated). The changes in beta 1 subunit expression occur in the absence of a detectable increase in expression of any of the three alpha subunit isoforms or in Na,K-ATPase activity. The selective induction of the expression of the beta subunit in avian myelomonocytic cells by 1,25(OH)2D3 reveals a previously unobserved feature of the regulation of Na,K-ATPase expression, while the targeting of beta subunit polypeptides to the plasma membrane in the absence of a corresponding increase in active Na,K-ATPase suggests that, in these cells, transport of the beta subunit to the plasma membrane may be independent of its binding to the alpha subunit.
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PMID:1,25-Dihydroxyvitamin D3 selectively induces increased expression of the Na,K-ATPase beta 1 subunit in avian myelomonocytic cells without a concomitant change in Na,K-ATPase activity. 925 43

In epithelial MDCK cells, the Na,K-ATPase is co-localized with adherens junctions in all stages of monolayer formation starting from initiation of cell-cell contact. The Na,K-ATPase and adherens junction proteins stay partially co-localized even after internalization due to disruption of intercellular contacts by Ca2+ deprivation. Similar to adherens junction proteins, the Na,K-ATPase is resistant to extraction with non-ionic detergent, suggesting pump association with the cytoskeleton. In contrast, the heterodimer formed by expressed unglycosylated Na,K-ATPase beta 1 subunit and the endogenous alpha 1 subunit is easily dissociated from the adherens junctions and cytoskeleton by detergent extraction. The MDCK cells in which half of the endogenous beta 1 subunits in the lateral membrane are substituted by unglycosylated beta 1 subunits display a slower rate of cell-to-cell contact formation and decreased ability to both spread over the surface and migrate. The lack of N-glycans in the Na,K-ATPase beta 1 subunit results in an impairment of mature cell-cell junctions as detected by an increase in the paracellular permeability of the MDCK cell monolayers and by a decrease in resistance of adherens junction proteins to extraction by a non-ionic detergent. Therefore the N-glycans of the Na,K-ATPase beta 1 subunit are important for retention of the pump at the sites of cell-cell contact. Moreover, they are important for the integrity and stability of cell-cell junctions in mature epithelia. In addition, N-glycans contribute to the formation of cell-cell contacts between surface-attached dispersed cells by mediating lamellipodia formation and stabilizing the newly formed adherens junctions.
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PMID:The roles of the Na,K-ATPase beta 1 subunit in pump sorting and epithelial integrity. 1800 Jul 47