Downregulation of Chloride Channel ClC-2 by Janus Kinase 3

Warsi, Jamshed; Elvira, Bernat; Hosseinzadeh, Zohreh; Shumilina, Ekaterina; Läng, Florian

doi:10.1007/s00232-014-9645-0

Cited by 12 publications

(8 citation statements)

References 54 publications

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“…JAK3 [20] and the related kinase JAK2 [21] are powerful regulators of Na + /K + ATPase and JAK3-deficient mice suffer from impaired renal tubular electrolyte retention and volume depletion [22]. Beyond that JAK3 contributes to the regulation of several carriers [23,24] and channels [25,26]]. …”

Section: Introductionmentioning

confidence: 99%

Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3

Warsi

Abousaab

Fezai

et al. 2015

Cell Physiol Biochem

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Background/Aims: Janus kinase 3 (JAK3), a kinase mainly expressed in hematopoietic cells, has been shown to down-regulate the Na⁺/K⁺ ATPase and participate in the regulation of several ion channels and carriers. Channels expressed in thymus and regulating the abundance of T lymphocytes include the voltage gated K⁺ channel KCNE1/KCNQ1. The present study explored whether JAK3 contributes to the regulation of KCNE1/KCNQ1. Methods: cRNA encoding KCNE1/KCNQ1 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type JAK3, constitutively active ^A568VJAK3, or inactive ^K851AJAK3. Voltage gated K⁺ channel activity was measured utilizing two electrode voltage clamp. Results: KCNE1/KCNQ1 activity was significantly increased by wild-type JAK3 and ^A568VJAK3, but not by ^K851AJAK3. The difference between oocytes expressing KCNE1/KCNQ1 alone and oocytes expressing KCNE1/KCNQ1 with ^A568VJAK3 was virtually abrogated by JAK3 inhibitor WHI-P154 (22 µM) but not by inhibition of transcription with actinomycin D (50 nM). Inhibition of KCNE1/KCNQ1 protein insertion into the cell membrane by brefeldin A (5 µM) resulted in a decline of the voltage gated current, which was similar in the absence and presence of ^A568VJAK3, suggesting that ^A568VJAK3 did not accelerate KCNE1/KCNQ1 protein retrieval from the cell membrane. Conclusion: JAK3 contributes to the regulation of membrane KCNE1/KCNQ1 activity, an effect sensitive to JAK3 inhibitor WHI-P154.

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Section: Introductionmentioning

confidence: 99%

Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3

Warsi

Abousaab

Fezai

et al. 2015

Cell Physiol Biochem

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“…The pleotropic effects of JAK3 include regulation of transport across the cell membrane [43,45,49,50,51,52,53,54] including the excitatory amino acid transporters [53] and the Na + /K + ATPase [49]. …”

Section: Introductionmentioning

confidence: 99%

Regulation of the Na<sup>+</sup>,Cl<sup>-</sup> Coupled Creatine Transporter CreaT (SLC6A8) by the Janus Kinase JAK3

2015

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Background: The creatine transporter CreaT (SLC6A8), a Na⁺,Cl^- coupled transporter is expressed in diverse tissues including the brain. Genetic defects of SLC6A8 result in mental retardation with seizures. The present study explored the regulation of CreaT by Janus kinase JAK3, which is expressed in a variety of tissues including the brain and participates in the regulation of cell survival and differentiation of neuronal precursor cells. Methods: CreaT was expressed in Xenopus laevis oocytes with or without wild-type JAK3, constitutively active ^A568VJAK3 and inactive ^K851AJAK3. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp. Results: Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes co-expression of JAK3 or ^A568VJAK3, but not co-expression of ^K851AJAK3 was followed by a significant decrease of creatine induced current. According to kinetic analysis JAK3 significantly decreased the maximal creatine transport rate. In CreaT and JAK3 expressing oocytes the creatine induced current was significantly increased by JAK3 inhibitor WHI-P154 (22 µM). Conclusion: JAK3 is a powerful negative regulator of the creatine transporter CreaT.

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“…JAK3 has previously been shown to participate in the regulation of a variety of further channels [70][71][72][73][74][75][76][77], transporters [78][79][80][81] and the Na + /K + ATPase [82]. The present study sheds additional light on the function of JAK3 as a transport regulating kinase.…”

Section: Discussionmentioning

confidence: 83%