Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3
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 v...
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Cell Physiol Biochem Press GmbH & Co KG
2015-12-01
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doaj-717d2996728541c690ed1c1060d4018d2020-11-25T02:40:28ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-12-013762476248510.1159/000438600438600Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3Jamshed WarsiAbeer AbousaabMyriam FezaiBernat ElviraFlorian LangBackground/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.http://www.karger.com/Article/FullText/438600OocytesVoltage clampJanus kinaseBrefeldinActinomycin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jamshed Warsi Abeer Abousaab Myriam Fezai Bernat Elvira Florian Lang |
spellingShingle |
Jamshed Warsi Abeer Abousaab Myriam Fezai Bernat Elvira Florian Lang Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3 Cellular Physiology and Biochemistry Oocytes Voltage clamp Janus kinase Brefeldin Actinomycin |
author_facet |
Jamshed Warsi Abeer Abousaab Myriam Fezai Bernat Elvira Florian Lang |
author_sort |
Jamshed Warsi |
title |
Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3 |
title_short |
Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3 |
title_full |
Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3 |
title_fullStr |
Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3 |
title_full_unstemmed |
Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3 |
title_sort |
regulation of voltage gated k+ channel kcne1/kcnq1 by the janus kinase jak3 |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2015-12-01 |
description |
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. |
topic |
Oocytes Voltage clamp Janus kinase Brefeldin Actinomycin |
url |
http://www.karger.com/Article/FullText/438600 |
work_keys_str_mv |
AT jamshedwarsi regulationofvoltagegatedkchannelkcne1kcnq1bythejanuskinasejak3 AT abeerabousaab regulationofvoltagegatedkchannelkcne1kcnq1bythejanuskinasejak3 AT myriamfezai regulationofvoltagegatedkchannelkcne1kcnq1bythejanuskinasejak3 AT bernatelvira regulationofvoltagegatedkchannelkcne1kcnq1bythejanuskinasejak3 AT florianlang regulationofvoltagegatedkchannelkcne1kcnq1bythejanuskinasejak3 |
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