Regulation of Taurine Transport Systems by Protein Kinase CK2 in Mammalian Cells

Lambert, Ian Henry; Hansen, Daniel Bloch

doi:10.1159/000335846

Cited by 29 publications

(45 citation statements)

References 125 publications

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“…CK2-mediated phosphorylation of PT inhibits the ER exit of PT protein, leading to reduced phosphate uptake ability in rice. These findings expand our understanding of CK2 function in plant growth and development and provide evidence for specific protein kinase effects on transmembrane proteins in plants as in animals (Ganley et al, 2001;Scott et al, 2006;Lambert and Hansen, 2011;Fu et al, 2013).…”

Section: Rice Ck2a3/b3 Functions As a Holoenzyme To Phosphorylate Pi mentioning

confidence: 52%

The Rice CK2 Kinase Regulates Trafficking of Phosphate Transporters in Response to Phosphate Levels

et al. 2015

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Phosphate transporters (PTs) mediate phosphorus uptake and are regulated at the transcriptional and posttranslational levels. In one key mechanism of posttranslational regulation, phosphorylation of PTs affects their trafficking from the endoplasmic reticulum (ER) to the plasma membrane. However, the kinase(s) mediating PT phosphorylation and the mechanism leading to ER retention of phosphorylated PTs remain unclear. In this study, we identified a rice (Oryza sativa) kinase subunit, CK2b3, which interacts with PT2 and PT8 in a yeast two-hybrid screen. Also, the CK2a3/b3 holoenzyme phosphorylates PT8 under phosphate-sufficient conditions. This phosphorylation inhibited the interaction of PT8 with PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1, a key cofactor regulating the exit of PTs from the ER to the plasma membrane. Additionally, phosphorus starvation promoted CK2b3 degradation, relieving the negative regulation of PT phosphorus-insufficient conditions. In accordance, transgenic expression of a nonphosphorylatable version of OsPT8 resulted in elevated levels of that protein at the plasma membrane and enhanced phosphorus accumulation and plant growth under various phosphorus regimes. Taken together, these results indicate that CK2a3/b3 negatively regulates PTs and phosphorus status regulates CK2a3/b3.

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Section: Rice Ck2a3/b3 Functions As a Holoenzyme To Phosphorylate Pi mentioning

confidence: 52%

The Rice CK2 Kinase Regulates Trafficking of Phosphate Transporters in Response to Phosphate Levels

et al. 2015

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“…Taurine (␤-amino-ethane sulfonic acid) is a metabolic inert amino acid that plays an important role in cell volume control, cellular metabolism, antioxidative defense, and initiation/progression of the apoptotic process (17, 23, 27-29, 31, 33, 54, 56, 57). Cellular taurine content is generally a balance between active uptake via the Na ϩ -and Cl Ϫ -dependent taurine transporter (TauT), passive release via volume-sensitive and volume-insensitive transporters (28), and in some cells (liver, pancreas, and testis) synthesis from cystein/methionine (31). Acute modulation of TauT activity involves Ser/Thr kinases (PKA, PKC, and CK2) and reactive oxygen species (ROS) (12,13,22,31,40,41,63), whereas long-term regulation of TauT activity involves transcriptional regulation by cellular osmo-sensing proteins (TonEBP, tonicity end-binding protein) and amino-sensing kinases (mTOR, mammalian target of rapamycin) (9,27,30,31).…”

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confidence: 99%

“…With the use of EATC and the human lung epithelial cell line A549, it has been demonstrated that swelling-induced activation of VSOAC involves phospholipase A 2 (PLA 2 ) and 5-lipoxygenase (5-LO) activity as well as binding of eicosanoids to the cysteinyl leukotriene 1 receptor CysLT1 (19,27). Once activated VSOAC activity is modulated by phosphatases, i.e., inhibition of vanadate-sensitive protein tyrosine phosphatases by ROS, which are generated in a variety of cells in response to osmotic perturbation, or inhibition of the phosphatidylinositol (3,4,5)-trisphosphate phosphatase PTEN (phosphatase and tensin homologue), leads to significant potentiation of taurine loss following exposure to hypotonic conditions (12,26,28,31). Key compounds of VSOAC have recently been identified as being members of the leucine-rich repeat containing 8 (LRRC8) family (49,62).…”

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confidence: 99%

Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate

Sørensen

Þorsteinsdóttir

Lambert

2014

American Journal of Physiology-Cell Physiology

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Sørensen BH, Thorsteinsdottir UA, Lambert IH. Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate. Am J Physiol Cell Physiol 307: C1071-C1080, 2014. First published September 24, 2014; doi:10.1152/ajpcell.00274.2014.-Cisplatin resistance is a major challenge in the treatment of cancer and develops through reduced drug accumulation and an increased ability to avoid drug-induced cell damage, cell shrinkage, and hence initiation of apoptosis. Uptake and release of the semiessential amino acid taurine contribute to cell volume homeostasis, and taurine has been reported to have antiapoptotic effects. Here we find that volume-sensitive taurine release in cisplatin-sensitive [wild-type (WT)] human ovarian cancer A2780 cells is reduced in the presence of the phospholipase A2 inhibitor bromenol lactone, the 5-lipoxygenase (5-LO) inhibitor ETH 615-139, and the cysteine leukotriene receptor 1 (CysLT1) antagonist zafirlukast and impaired by the anion channel blocker DIDS (4,4=-diisothiocyanatostilbene-2,2=-disulfonate). Comparing WT and cisplatin-resistant (RES) A2780 cells we also find that evasion of cisplatin-induced cell death in RES A2780 cells correlates with an increased accumulation of taurine, due to an increased taurine uptake and a concomitant impairment of the volume-sensitive taurine release pathway, as well an inability to reduce cell volume after osmotic cell swelling. Downregulation of volume-sensitive taurine release in RES A2780 cells correlates with reduced expression of the leucine-rich repeat-containing protein 8A (LRRC8A). Furthermore, acute (18 h) exposure to cisplatin (5-10 M) increases taurine release and LRRC8A expression in WT A2780 cells whereas cisplatin has no effect on LRRC8A expression in RES A2780 cells. It is suggested that shift in LRRC8A activity can be used as biomarker for apoptotic progress and acquirement of drug resistance. key word: platinum drugs; drug resistance; cell volume regulation; LRRC8A; TauT OVARIAN CANCER IS A LEADING cause of death among gynecological cancer patients, and the 5-yr survival rate has been estimated to 30% (64). The main reasons for the failure in treatment outcome are that 70% of the patients have already reached advanced stages of cancer progression at the time of diagnosis, i.e., the cancer has already spread within the pelvis and abdomen (68) and that most ovarian cancer cells rapidly develop resistance or multidrug resistance (MDR) against the chemotherapy.Cisplatin and chemotherapeutic resistance. Cisplatin was the first member of a class of platinum-based anticancer drugs, which also includes carboplatin and oxaliplatin (7,25), and today cisplatin is frequently used in chemotherapeutic treatment of ovarian cancer, lung cancer, and lymphomas (60). Cisplatin is administered to cancer patients intravenously as a sterile saline solution. Once circulating in the bloodstream, cisplatin is taken up by the cells and accumulated in the cell nucleus, where it causes DNA l...

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“…The cellular taurine content is a balance between endogenous synthesis, active uptake via 1) the Na ϩ -and Cl Ϫ -dependent transporter TauT (SLC6A6) or 2) the H ϩ -coupled, pH-dependent, Na ϩ -and Cl Ϫ -independent amino acid transporter PAT1 (SLC36A1), and passive release via 1) a volume-sensitive leak pathway, activated by osmotic cell swelling, designated volume-sensitive organic anion channel (VSOAC) (34,36); or 2) a volume-insensitive leak pathways activated during apoptosis (55), cholesterol depletion (67), and anoxia (49). The cellular taurine concentration ranges from 10 mM, e.g., in fibroblasts, to 40 -50 mM in Ehrlich ascites cells (34).…”

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confidence: 99%

“…Translocation of one taurine molecule across the plasma membrane via TauT involves two to three Na ions and acute modulation of TauT activity by protein kinases (PKA, PKC, CK2) and ROS involves shift in TauT's substrate affinity, transport capacity, and/or the Na:taurine stoichiometry (13,14,19,45,69). Passive taurine release from cells via VSOAC activation involves 1) mobilization of arachidonic acid from the nuclear envelope by cell-specific PLA 2 subtypes (52,53), ROS generation by NADPH oxidases (8,34), and fatty acid oxidation to leukotrienes by 5-lipoxygenase (5-LO) (38); 2) increased tyrosine kinase activity (34,51); and 3) activation of protein kinases normally related to growth factor signaling, i.e., phosphatidylinositol 3-kinase (PI3K), Akt, and glycogen synthase kinase 3␤ (GSK3␤) (36).…”

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confidence: 99%

Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549: role of the 5-lipoxygenase

Holm

Grygorczyk

Lambert

2013

American Journal of Physiology-Cell Physiology

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Holm JB, Grygorczyk R, Lambert IH. Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549: role of the 5-lipoxygenase. Am J Physiol Cell Physiol 305: C48-C60, 2013. First published March 13, 2013; doi:10.1152/ajpcell.00412.2012.-Pathophysiological conditions challenge cell volume homeostasis and perturb cell volume regulatory mechanisms leading to alterations of cell metabolism, active transepithelial transport, cell migration, and death. We report that inhibition of the 5-lipoxygenase (5-LO) with AA861 or ETH 615-139, the cysteinyl leukotriene 1 receptor (CysLT1) with the antiasthmatic drug Zafirlukast, or the volume-sensitive organic anion channel (VSOAC) with DIDS blocks the release of organic osmolytes (taurine, meAIB) and the concomitant cell volume restoration following hypoosmotic swelling of human type II-like lung epithelial cells (A549). Reactive oxygen species (ROS) are produced in A549 cells upon hypotonic cell swelling by a diphenylene iodonium-sensitive NADPH oxidase. The swelling-induced taurine release is suppressed by ROS scavenging (butylated hydroxytoluene, N-acetyl cysteine) and potentiated by H 2O2. Ca 2ϩ mobilization with ionomycin or ATP stimulates the swelling-induced taurine release whereas calmodulin inhibition (W7) inhibits the release. Chelation of the extracellular Ca 2ϩ (EGTA) had no effect on swelling-induced taurine release but prevented ATP-induced stimulation. H2O2, ATP, and ionomycin were unable to stimulate the taurine release in the presence of AA861 or Zafirlukast, placing 5-LO and CysLT1 as essential elements in the swelling-induced activation of VSOAC with ROS and Ca 2ϩ as potent modulators. Inhibition of tyrosine kinases (genistein, cucurbitacin) reduces volume-sensitive taurine release, adding tyrosine kinases (Janus kinase) as regulators of VSOAC activity. Caspase-3 activity during hypoxia is unaffected by inhibition of 5-LO/CysLT1 but reduced when swelling-induced taurine loss via VSOAC is prevented by DIDS excess extracellular taurine, indicating a beneficial role of taurine under hypoxia. 5-lipoxygenase; lung adenocarcinoma; cysteinyl leukotriene 1 receptor; hypoxia; ischemia; cell volume regulation; reactive oxygen species; taurine homeostasis WITHIN RECENT YEARS it has become clear that cell volume regulation under isotonic conditions and cell volume restoration following osmotic perturbations are important for regulation of the intracellular milieu and cellular functions, such as cell metabolism, cell migration, and control of cell death (see refs. 16, 39). Cells maintain a steady cell volume by regulating the intracellular concentrations of ions (mainly Na ϩ , K ϩ , and Cl Ϫ ) and organic osmolytes (16,39). A consequence of hypotonic cell swelling is net loss of KCl and amino acids including the ␤-amino ethane sulfonic acid, taurine.Taurine: a multifunctional amino acid. Taurine is the most abundant free amino acid of the human body and has been estimated to account for up to 38% of the total free amino acid pool in rat heart ce...

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Regulation of Taurine Transport Systems by Protein Kinase CK2 in Mammalian Cells

Cited by 29 publications

References 125 publications

The Rice CK2 Kinase Regulates Trafficking of Phosphate Transporters in Response to Phosphate Levels

The Rice CK2 Kinase Regulates Trafficking of Phosphate Transporters in Response to Phosphate Levels

Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate

Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549: role of the 5-lipoxygenase

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