title: Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  JAK3 contributes to the regulation of membrane KCNE1/KCNQ1 activity, an effect sensitive to JAK3 inhibitor WHI-P154.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Warsi
authors.forename: Abeer
authors.initials: A
authors.lastname: Abousaab
authors.forename: Myriam
authors.initials: M
authors.lastname: Fezai
authors.forename: Bernat
authors.initials: B
authors.lastname: Elvira
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D053616:Janus Kinase 3 / Q000378:metabolism*; D051657:KCNQ1 Potassium Channel / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: C530745:KCNE1 protein, Xenopus; D051657:KCNQ1 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D029867:Xenopus Proteins; D053616:Janus Kinase 3