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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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-12-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/438600 |
| _version_ | 1828161500066349056 |
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| author | Jamshed Warsi Abeer Abousaab Myriam Fezai Bernat Elvira Florian Lang |
| author_facet | Jamshed Warsi Abeer Abousaab Myriam Fezai Bernat Elvira Florian Lang |
| author_sort | Jamshed Warsi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T00:39:36Z |
| format | Article |
| id | doaj.art-717d2996728541c690ed1c1060d4018d |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-12T00:39:36Z |
| publishDate | 2015-12-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-717d2996728541c690ed1c1060d4018d2022-12-22T03:55:03ZengCell 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 |
| 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 |
| title | 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_short | 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 |
| topic | Oocytes Voltage clamp Janus kinase Brefeldin Actinomycin |
| url | http://www.karger.com/Article/FullText/438600 |
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