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Transmembrane segment XI of the na+/H+ antiporter of S. pombe is a critical part of the ion translocation pore
Download2017-01-01
Dutta, Debajyoti, Shin, Kyungsoo, Rainey, Jan K., Fliegel, Larry
The Na+/H+ exchanger of the plasma membrane of S. pombe (SpNHE1) removes intracellular sodium in exchange for an extracellular proton. We examined the structure and functional role of amino acids 360–393 of putative transmembrane (TM) segment XI of SpNHE1. Structural analysis suggested that it...
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2016-01-01
Amith, Schammim Ray, Fliegel, Larry
Introduction: Triple-negative breast cancer, in which cells lack the expression of estrogen, progesterone, and human epidermal growth factor 2 receptors, is a clinical subtype of breast cancer commonly associated with poor prognosis. It tends to be aggressively metastatic with a high recurrence...
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Na+/H+ exchanger NHE1 regulation modulates metastatic potential and epithelial-mesenchymal transition of triple-negative breast cancer cells
Download2016-01-01
Amith, Schammim Ray, Wilkinson, Jodi Marie, Fliegel, Larry
In triple-negative breast cancer (TNBC), the high recurrence rate, increased invasion and aggressive metastatic formation dictate patient survival. We previously demonstrated a critical role for the Na+/H+ exchanger isoform 1 (NHE1) in controlling metastasis of triple-negative cells. Here, we...
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Stop codon polymorphisms in the human SLC9A1 gene disrupt or compromise na+/H+ exchanger function
Download2016-01-01
Li, Xiuju J., Augustine, Aruna, Chen, Shuo, Fliegel, Larry
The NHE1 isoform of the mammalian Na+/H+ exchanger is a ubiquitous plasma membrane protein that regulates intracellular pH in mammalian cells by removing one intracellular proton in exchange for one extracellular sodium. Deletion of the NHE1 gene (SLC9A1) affects the growth and motor ability of...
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Na+/H+ exchanger isoform 1-induced osteopontin expression facilitates cardiomyocyte hypertrophy
Download2015-01-01
Mohamed, Iman A., Gadeau, Alain-Pierre, Fliegel, Larry, Lopaschuk, Gary, Mlih, Mohamed, Abdulrahman, Nabeel, Filmore, Natasha, Mraiche, Fatima
Enhanced expression and activity of the Na+/H+ exchanger isoform 1 (NHE1) has been implicated in cardiomyocyte hypertrophy in various experimental models. The upregulation of NHE1 was correlated with an increase in osteopontin (OPN) expression in models of cardiac hypertrophy (CH), and the...
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A novel human mutation in the SLC9A1 gene results in abolition of na+/H+ exchanger activity
Download2015-01-01
The SLC9A1 gene, the Na+/H+ exchanger isoform 1 is the principal plasma membrane Na+/H+ exchanger of mammalian cells and functions by exchanging one intracellular proton for one extracellular sodium. The human protein is 815 amino acids in length. Five hundred N-terminal amino acids make up the...
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Na+/H+ exchange in the tumour microenvironment: Does NHE1 drive breast cancer carcinogenesis?
Download2015-01-01
Amith, Schammim Ray, Fong, Sunny, Baksh, Shairaz, Fliegel, Larry
Ionic messengers signal several critical events in carcinogenesis, including metastasis, the leading cause of patient mortality. The aberrant metabolic, proliferative and anti-apoptotic nature of neoplastic cells can be traced to the abnormal expression of their ion transporters and related...
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The na+/H+ exchanger (NHE1) as a novel co-adjuvant target in paclitaxel therapy of triple-negative breast cancer cells
Download2015-01-01
Amith, Schammim Ray, Wilkinson, Jodi Marie, Baksh, Shairaz, Fliegel, Larry
Dysregulation of Na+/H+ exchanger isoform one (NHE1) activity is a hallmark of cells undergoing tumorigenesis and metastasis, the leading cause of patient mortality. The acidic tumor microenvironment is thought to facilitate the development of resistance to chemotherapy drugs and to promote...
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Structural and functional analysis of transmembrane segment IV of the salt tolerance protein Sod2
Download2013-01-01
Ullah, Assad, Kemp, Grant, Lee, Brian, Alves, Claudia, Young, Howard, Sykes, Brian D., Fliegel, Larry
Sod2 is the plasma membrane Na+/H+ exchanger of the fission yeast Schizosaccharomyces pombe. It provides salt tolerance by removing excess intracellular sodium (or lithium) in exchange for protons. We examined the role of amino acid residues of transmembrane segment IV (TM IV)...
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2011-01-01
Karki, Pratap, Li, Xiuju J., Schrama, David, Fliegel, Larry
The serine/threonine kinase B-Raf is the second most frequently occurring human oncogene after Ras. Mutations of B-Raf occur with the highest incidences in melanoma, and the most common mutant, V600E, renders B-Raf constitutively active. The sodium proton exchanger isoform 1 (NHE1) is a...