Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Membr Biol
2015 Dec 01;2486:1061-70. doi: 10.1007/s00232-015-9817-6.
Show Gene links
Show Anatomy links
Regulation of Voltage-Gated K+ Channel Kv1.5 by the Janus Kinase JAK3.
Warsi J
,
Elvira B
,
Bissinger R
,
Hosseinzadeh Z
,
Lang F
.
???displayArticle.abstract???
The tyrosine kinase Janus kinase 3 (JAK3) participates in the regulation of cell proliferation and apoptosis. The kinase further influences ion channels and transport proteins. The present study explored whether JAK3 contributes to the regulation of the voltage-gated K(+) channel Kv1.5, which participates in the regulation of diverse functions including atrial cardiac action potential and tumor cell proliferation. To this end, cRNA encoding Kv1.5 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type JAK3, constitutively active (A568V)JAK3, or inactive (K851A)JAK3. Voltage-gated K(+) channel activity was measured utilizing dual electrode voltage clamp, and Kv1.5 channel protein abundance in the cell membrane was quantified utilizing chemiluminescence of Kv1.5 containing an extracellular hemagglutinin epitope (Kv1.5-HA). As a result, Kv1.5 activity and Kv1.5-HA protein abundance were significantly decreased by wild-type JAK3 and (A568V)JAK3, but not by (K851A)JAK3. Inhibition of Kv1.5 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 (A568V)JAK3, suggesting that (A568V)JAK3 did not accelerate Kv1.5 protein retrieval from the cell membrane. A 24 h treatment with ouabain (100 µM) significantly decreased the voltage-gated current in oocytes expressing Kv1.5 without or with (A568V)JAK3 and dissipated the difference between oocytes expressing Kv1.5 alone and oocytes expressing Kv1.5 with (A568V)JAK3. In conclusion, JAK3 contributes to the regulation of membrane Kv1.5 protein abundance and activity, an effect sensitive to ouabain and thus possibly involving Na(+)/K(+) ATPase activity.
Almilaji,
Down-regulation of Na/K+ atpase activity by human parvovirus B19 capsid protein VP1.
2013, Pubmed,
Xenbase
Almilaji,
Down-regulation of Na/K+ atpase activity by human parvovirus B19 capsid protein VP1.
2013,
Pubmed
,
Xenbase
Almilaji,
Upregulation of Na+,Cl(-)-coupled betaine/γ-amino-butyric acid transporter BGT1 by Tau tubulin kinase 2.
2013,
Pubmed
,
Xenbase
Almilaji,
Upregulation of the creatine transporter Slc6A8 by Klotho.
2014,
Pubmed
,
Xenbase
Archer,
Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer.
2008,
Pubmed
Barfield,
Characterization of potassium channels involved in volume regulation of human spermatozoa.
2005,
Pubmed
Barfield,
The effects of putative K+ channel blockers on volume regulation of murine spermatozoa.
2005,
Pubmed
Bharadwaj,
Transcription factors in the control of dendritic cell life cycle.
2007,
Pubmed
Bhavsar,
Janus kinase 3 is expressed in erythrocytes, phosphorylated upon energy depletion and involved in the regulation of suicidal erythrocyte death.
2011,
Pubmed
Bhavsar,
Energy-sensitive regulation of Na+/K+-ATPase by Janus kinase 2.
2014,
Pubmed
,
Xenbase
Bilodeau,
Kv1.5 blockers for the treatment of atrial fibrillation: approaches to optimization of potency and selectivity and translation to in vivo pharmacology.
2009,
Pubmed
Bonnet,
The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted.
2007,
Pubmed
Brendel,
Blockers of the Kv1.5 channel for the treatment of atrial arrhythmias.
2003,
Pubmed
Comes,
The voltage-dependent K(+) channels Kv1.3 and Kv1.5 in human cancer.
2013,
Pubmed
Cornejo,
JAK3: a two-faced player in hematological disorders.
2009,
Pubmed
Dërmaku-Sopjani,
Down-regulation of the Na+-coupled phosphate transporter NaPi-IIa by AMP-activated protein kinase.
2013,
Pubmed
,
Xenbase
Elvira,
SPAK and OSR1 dependent down-regulation of murine renal outer medullary K channel ROMK1.
2014,
Pubmed
,
Xenbase
Fainstein,
Neural precursor cells inhibit multiple inflammatory signals.
2008,
Pubmed
Felipe,
Targeting the voltage-dependent K(+) channels Kv1.3 and Kv1.5 as tumor biomarkers for cancer detection and prevention.
2012,
Pubmed
Felipe,
Influence of cloned voltage-gated K+ channel expression on alanine transport, Rb+ uptake, and cell volume.
1993,
Pubmed
Fezai,
Negative regulation of the creatine transporter SLC6A8 by SPAK and OSR1.
2014,
Pubmed
,
Xenbase
Ghoreschi,
Janus kinases in immune cell signaling.
2009,
Pubmed
González,
Kv1.5-Kv beta interactions: molecular determinants and pharmacological consequences.
2010,
Pubmed
Haan,
Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptors.
2011,
Pubmed
Hosseinzadeh,
Down-regulation of the epithelial Na⁺ channel ENaC by Janus kinase 2.
2014,
Pubmed
,
Xenbase
Hosseinzadeh,
Upregulation of peptide transporters PEPT1 and PEPT2 by Janus kinase JAK2.
2013,
Pubmed
,
Xenbase
Hosseinzadeh,
The Role of Janus Kinase 3 in the Regulation of Na⁺/K⁺ ATPase under Energy Depletion.
2015,
Pubmed
,
Xenbase
Hosseinzadeh,
Downregulation of KCNQ4 by Janus kinase 2.
2013,
Pubmed
,
Xenbase
Imada,
The Jak-STAT pathway.
2000,
Pubmed
Kim,
MS-1020 is a novel small molecule that selectively inhibits JAK3 activity.
2010,
Pubmed
Lang,
Potassium channels in renal epithelial transport regulation.
1992,
Pubmed
Lang,
Ion channels in cancer: future perspectives and clinical potential.
2014,
Pubmed
Lang,
Role of ion transport in control of apoptotic cell death.
2012,
Pubmed
Leanza,
Correlation between potassium channel expression and sensitivity to drug-induced cell death in tumor cell lines.
2014,
Pubmed
Leanza,
Induction of apoptosis in macrophages via Kv1.3 and Kv1.5 potassium channels.
2012,
Pubmed
Malinge,
Activating mutations in human acute megakaryoblastic leukemia.
2008,
Pubmed
Messner,
Ouabain decreases apparent potassium-conductance in proximal tubules of the amphibian kidney.
1985,
Pubmed
Mia,
Downregulation of Kv1.5 K channels by the AMP-activated protein kinase.
2012,
Pubmed
,
Xenbase
Munoz,
Up-regulation of the inwardly rectifying K⁺ channel Kir2.1 (KCNJ2) by protein kinase B (PKB/Akt) and PIKfyve.
2013,
Pubmed
,
Xenbase
Nakayama,
BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3.
2009,
Pubmed
O'Shea,
Jak3 and the pathogenesis of severe combined immunodeficiency.
2004,
Pubmed
O'Shea,
Cytokine signaling in 2002: new surprises in the Jak/Stat pathway.
2002,
Pubmed
Pakladok,
PIKfyve sensitivity of hERG channels.
2013,
Pubmed
,
Xenbase
Pakladok,
Upregulation of the Na⁺-coupled phosphate cotransporters NaPi-IIa and NaPi-IIb by B-RAF.
2014,
Pubmed
,
Xenbase
Pardo,
The roles of K(+) channels in cancer.
2014,
Pubmed
Shuai,
Regulation of JAK-STAT signalling in the immune system.
2003,
Pubmed
Suessbrich,
The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Tamargo,
I(Kur)/Kv1.5 channel blockers for the treatment of atrial fibrillation.
2009,
Pubmed
Turner,
Cl- and K+ channels and their role in primary brain tumour biology.
2014,
Pubmed
Uckun,
Targeting JAK3 tyrosine kinase-linked signal transduction pathways with rationally-designed inhibitors.
2007,
Pubmed
Umbach,
Intestinal Na+ loss and volume depletion in JAK3-deficient mice.
2013,
Pubmed
Vijayakrishnan,
Treating inflammation with the Janus kinase inhibitor CP-690,550.
2011,
Pubmed
Walters,
Activating alleles of JAK3 in acute megakaryoblastic leukemia.
2006,
Pubmed
Wang,
Sequential activation of JAKs, STATs and xanthine dehydrogenase/oxidase by hypoxia in lung microvascular endothelial cells.
2008,
Pubmed
Wang,
JAK-STAT signaling pathway in pulmonary arterial smooth muscle cells is activated by hypoxia.
2005,
Pubmed
Warsi,
Downregulation of peptide transporters PEPT1 and PEPT2 by oxidative stress responsive kinase OSR1.
2014,
Pubmed
,
Xenbase
Warsi,
SPAK dependent regulation of peptide transporters PEPT1 and PEPT2.
2014,
Pubmed
,
Xenbase
Warsi,
Effect of Janus kinase 3 on the peptide transporters PEPT1 and PEPT2.
2013,
Pubmed
,
Xenbase
Warsi,
Regulation of ClC-2 activity by SPAK and OSR1.
2014,
Pubmed
,
Xenbase
Yeung,
Potassium channels involved in human sperm volume regulation--quantitative studies at the protein and mRNA levels.
2008,
Pubmed
de Totero,
The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways.
2008,
Pubmed
