title: Up-regulation of Kv1.3 channels by janus kinase 2.
abstract: The janus-activated kinase 2 JAK2 participates in the signalling of several hormones including interferon, a powerful regulator of lymphocyte function. Lymphocyte activity and survival depend on the activity of the voltage-gated K(+) channel KCNA3 (Kv1.3). The present study thus explored whether JAK2 modifies the activity of voltage-gated K(+) channel KCNA3. To this end, cRNA encoding KCNA3 was injected in Xenopus oocytes with or without additional injection of cRNA encoding wild-type human JAK2, human inactive (K882E)JAK2 mutant, or human gain-of-function (V617F)JAK2 mutant. KCNA3-dependent depolarization-induced current was determined utilizing dual-electrode voltage clamp, and protein KCNA3 abundance in the cell membrane was quantified by chemiluminescence. Moreover, the effect of interferon-γ on voltage-gated K(+) current was determined by patch clamp in mainly KCNA3-expressing Jurkat T cells with or without prior treatment with JAK2 inhibitor AG490 (40 µM). As a result, KCNA3 channel activity and protein abundance were up-regulated by coexpression of JAK2 or (V617F)JAK2 but not (K882E)JAK2. The effect of JAK2 coexpression was reversed by AG490 treatment. In human Jurkat T lymphoma cells, voltage-gated K(+) current was up-regulated by interferon-γ and down-regulated by AG490 (40 µM). In conclusion, JAK2 participates in the signalling, regulating the voltage-gated K(+) channel KCNA3.
authors: Department of Physiology, Institute of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.
authors: Zohreh
authors: Z
authors: Hosseinzadeh
authors: Jamshed
authors: J
authors: Warsi
authors: Bernat
authors: B
authors: Elvira
authors: Ahmad
authors: A
authors: Almilaji
authors: Ekaterina
authors: E
authors: Shumilina
authors: Florian
authors: F
authors: Lang
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D051664:Kv1.3 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D015854:Up-Regulation; D014981:Xenopus
chemical_list: D051664:Kv1.3 Potassium Channel; D053614:Janus Kinase 2
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