title: Regulation of Large Conductance Voltage-and Ca2+-Activated K+ Channels by the Janus Kinase JAK3.
abstract: OBJECTIVE
  Janus kinase 3 (JAK3), a tyrosine kinase contributing to the regulation of cell proliferation and apoptosis of lymphocytes and tumour cells, has been shown to modify the expression and function of several ion channels and transport proteins. Channels involved in the regulation of cell proliferation include the large conductance voltage- and Ca(2+)-activated K(+) channel BK. The present study explored whether JAK3 modifies BK channel protein abundance and current.
  
  
  METHODS
  cRNA encoding Ca(2+)-insensitive BK channel (BK(M513I+Δ899-903)) was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type JAK3, constitutively active A568VJAK3, or inactive (K851A)JAK3. Voltage gated K(+ )channel activity was measured utilizing dual electrode voltage clamp. Moreover, BK channel protein abundance was determined utilizing flow cytometry in CD19(+) B lymphocyte cell membranes from mice lacking functional JAK3 (jak3(-/-)) and corresponding wild-type mice (jak3(+/+)).
  
  
  RESULTS
  BK activity in BK(M513I+Δ899-903) expressing oocytes was slightly but significantly decreased by coexpression of wild-type JAK3 and of (A568V)JAK3, but not by coexpression of (K851A)JAK3. The BK channel protein abundance in the cell membrane was significantly higher in jak3(-/-) than in jak3(+/+) B lymphocytes. The decline of conductance in BK and JAK3 coexpressing oocytes following inhibition of channel protein insertion by brefeldin A (5 µM) was similar in oocytes expressing BK with JAK3 and oocytes expressing BK alone, indicating that JAK3 might slow channel protein insertion into rather than accelerating channel protein retrieval from the cell membrane.
  
  
  CONCLUSIONS
  JAK3 is a weak negative regulator of membrane BK protein abundance and activity.
authors: Department of Physiology I, University of Tx00FC;bingen, Tx00FC;bingen, Germany.
authors: Jamshed
authors: J
authors: Warsi
authors: Yogesh
authors: Y
authors: Singh
authors: Bernat
authors: B
authors: Elvira
authors: Zohreh
authors: Z
authors: Hosseinzadeh
authors: Florian
authors: F
authors: Lang
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D020126:Brefeldin A / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D053616:Janus Kinase 3 / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D051036:Large-Conductance Calcium-Activated Potassium Channels; D020126:Brefeldin A; D053616:Janus Kinase 3