Down-Regulation of the Myoinositol Transporter SMIT by JAK2

Hosseinzadeh, Zohreh; Bhavsar, Shefalee K.; Läng, Florian

doi:10.1159/000343335

Cited by 19 publications

(12 citation statements)

References 56 publications

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“…Cell survival during energy depletion critically depends on electrolyte transport across the cell membrane (47), as ATP is required for the function of the Na ϩ /K ϩ -ATPase (75). Recently, JAK2 has been shown to upregulate Cl Ϫ channels (40), the Na ϩ -coupled glucose transporter SLC5A1 (41), several Na ϩ -coupled amino acid transporters (11,41), the betaine/ GABA transporter BGT1 (43), and the Na myoinositol transporter SMIT (39). JAK2 downregulates the Na ϩ -coupled creatine transporter SLC6A8 (73).…”

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confidence: 99%

Energy-sensitive regulation of Na⁺/K⁺-ATPase by Janus kinase 2

Bhavsar

Hosseinzadeh

Brenner

et al. 2014

American Journal of Physiology-Cell Physiology

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Janus kinase 2 (JAK2) contributes to intracellular signaling of leptin and erythropoietin, hormones protecting cells during energy depletion. The present study explores whether JAK2 is activated by energy depletion and regulates Na+/K+-ATPase, the major energy-consuming pump. In Jurkat cells, JAK2 activity was determined by radioactive kinase assay, phosphorylated JAK2 detected by Western blotting, ATP levels measured by luciferase assay, as well as Na+/K+-ATPase α1-subunit transcript and protein abundance determined by real-time PCR and Western blotting, respectively. Ouabain-sensitive K+-induced currents ( Ipump) were measured by whole cell patch clamp. Ipump was further determined by dual-electrode voltage clamp in Xenopus oocytes injected with cRNA-encoding JAK2, active V617FJAK2, or inactive K882EJAK2. As a result, in Jurkat T cells, JAK2 activity significantly increased following energy depletion by sodium azide (NaN3) or 2,4- dinitro phenol (DNP). DNP- and NaN3-induced decrease of cellular ATP was significantly augmented by JAK2 inhibitor AG490 and blunted by Na+/K+-ATPase inhibitor ouabain. DNP decreased and AG490 enhanced Ipump as well as Na+/K+-ATPase α1-subunit transcript and protein abundance. The α1-subunit transcript levels were also enhanced by signal transducer and activator of transcription-5 inhibitor CAS 285986-31-4. In Xenopus oocytes, Ipump was significantly decreased by expression of JAK2 and V617FJAK2 but not of K882EJAK2, effects again reversed by AG490. In V617FJAK2-expressing Xenopus oocytes, neither DNP nor NaN3 resulted in further decline of Ipump. In Xenopus oocytes, the effect of V617FJAK2 on Ipump was not prevented by inhibition of transcription with actinomycin. In conclusion, JAK2 is a novel energy-sensing kinase that curtails energy consumption by downregulating Na+/K+-ATPase expression and activity.

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confidence: 99%

Energy-sensitive regulation of Na⁺/K⁺-ATPase by Janus kinase 2

Bhavsar

Hosseinzadeh

Brenner

et al. 2014

American Journal of Physiology-Cell Physiology

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“…The flow rate of the superfusion was approx. 20 ml/min, and a complete exchange of the bath solution was reached within about 10 s [45,46]. …”

Section: Methodsmentioning

confidence: 99%

SPAK Dependent Regulation of Peptide Transporters PEPT1 and PEPT2

Warsi

Luo

Elvira

et al. 2014

Kidney Blood Press Res

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Background/Aims: SPAK (STE20-related proline/alanine-rich kinase) is a powerful regulator of renal tubular ion transport and blood pressure. Moreover, SPAK contributes to the regulation of cell volume. Little is known, however, about a role of SPAK in the regulation or organic solutes. The present study thus addressed the influence of SPAK on the peptide transporters PEPT1 and PEPT2. Methods: To this end, cRNA encoding PEPT1 or PEPT2 were injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type, SPAK, WNK1 insensitive inactive ^T233ASPAK, constitutively active ^T233ESPAK, and catalytically inactive ^D212ASPAK. Electrogenic peptide (glycine-glycine) transport was determined by dual electrode voltage clamp and PEPT2 protein abundance in the cell membrane by chemiluminescence. Intestinal electrogenic peptide transport was estimated from peptide induced current in Ussing chamber experiments of jejunal segments isolated from gene targeted mice expressing SPAK resistant to WNK-dependent activation (spak^tg/tg) and respective wild-type mice (spak^+/+). Results: In PEPT1 and in PEPT2 expressing oocytes, but not in oocytes injected with water, the dipeptide gly-gly (2 mM) generated an inward current, which was significantly decreased following coexpression of SPAK. The effect of SPAK on PEPT1 was mimicked by ^T233ESPAK, but not by ^D212ASPAK or ^T233ASPAK. SPAK decreased maximal peptide induced current of PEPT1. Moreover, SPAK decreased carrier protein abundance in the cell membrane of PEPT2 expressing oocytes. In intestinal segments gly-gly generated a current, which was significantly higher in spak^tg/tg than in spak^+/+ mice. Conclusion: SPAK is a powerful regulator of peptide transporters PEPT1 and PEPT2.

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“…Xenopus oocytes were prepared as previously described [46]. cRNA encoding K ir 2.1 (10 ng) was injected with or without 1, 3 or 10 ng of cRNA encoding either wild type human SGK3, constitutively active S419D SGK3 or inactive K191N SGK3 on the day of preparation of the Xenopus oocytes [47].…”

Section: Methodsmentioning

confidence: 99%

Up-Regulation of K_ir2.1 (KCNJ2) by the Serum & Glucocorticoid Inducible SGK3

Muñoz

Pakladok²,

Almilaji³

et al. 2014

Cell Physiol Biochem

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Background/Aims: The serum & glucocorticoid inducible kinase SGK3, an ubiquitously expressed serine/threonine kinase, regulates a variety of ion channels. It has previously been shown that SGK3 upregulates the outwardly rectifying K⁺ channel K_V11.1, which is expressed in cardiomyocytes. Cardiomyocytes further express the inward rectifier K⁺ channel K_ir2.1, which contributes to maintenance of resting cell membrane potential. Loss-of-function mutations of KCNJ2 encoding K_ir2.1 result in Andersen-Tawil syndrome with periodic paralysis, cardiac arrhythmia and dysmorphic features. The present study explored whether SGK3 participates in the regulation of K_ir2.1. Methods: cRNA encoding K_ir2.1 was injected into Xenopus oocytes with and without additional injection of cRNA encoding wild type SGK3, constitutively active ^S419DSGK3 or inactive ^K191NSGK3. K_ir2.1 activity was determined by two-electrode voltage-clamp and K_ir2.1 protein abundance in the cell membrane by immunostaining and subsequent confocal imaging or by chemiluminescence. Results: Injection of 10 ng cRNA encoding wild type SGK3 and ^S419DSGK3, but not ^K191NSGK3 significantly enhanced K_ir2.1-mediated currents. SGK inhibitor EMD638683 (50 µM) abrogated ^S419DSGK3-induced up-regulation of K_ir2.1. Moreover, wild type SGK3 enhanced the channel protein abundance in the cell membrane. The decay of K_ir2.1-mediated currents following inhibition of channel insertion into the cell membrane by brefeldin A (5 µM) was similar in oocytes coexpressing K_ir2.1 and SGK3 as in oocytes expressing K_ir2.1 alone, suggesting that SGK3 influences channel insertion into rather than channel retrieval from the cell membrane. Conclusions: SGK3 is a novel regulator of K_ir2.1.

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Down-Regulation of the Myoinositol Transporter SMIT by JAK2

Cited by 19 publications

References 56 publications

Energy-sensitive regulation of Na⁺/K⁺-ATPase by Janus kinase 2

Energy-sensitive regulation of Na⁺/K⁺-ATPase by Janus kinase 2

SPAK Dependent Regulation of Peptide Transporters PEPT1 and PEPT2

Up-Regulation of K_ir2.1 (KCNJ2) by the Serum & Glucocorticoid Inducible SGK3

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Down-Regulation of the Myoinositol Transporter SMIT by JAK2

Cited by 19 publications

References 56 publications

Energy-sensitive regulation of Na+/K+-ATPase by Janus kinase 2

Energy-sensitive regulation of Na+/K+-ATPase by Janus kinase 2

SPAK Dependent Regulation of Peptide Transporters PEPT1 and PEPT2

Up-Regulation of Kir2.1 (KCNJ2) by the Serum & Glucocorticoid Inducible SGK3

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Energy-sensitive regulation of Na⁺/K⁺-ATPase by Janus kinase 2

Energy-sensitive regulation of Na⁺/K⁺-ATPase by Janus kinase 2

Up-Regulation of K_ir2.1 (KCNJ2) by the Serum & Glucocorticoid Inducible SGK3