| First Author | Hosseinzadeh Z | Year | 2015 |
| Journal | J Membr Biol | Volume | 248 |
| Issue | 2 | Pages | 309-17 |
| PubMed ID | 25644777 | Mgi Jnum | J:352396 |
| Mgi Id | MGI:6877922 | Doi | 10.1007/s00232-015-9772-2 |
| Citation | Hosseinzadeh Z, et al. (2015) Up-regulation of Kv1.3 channels by janus kinase 2. J Membr Biol 248(2):309-17 |
| abstractText | 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-gamma 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 microM). 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-gamma and down-regulated by AG490 (40 microM). In conclusion, JAK2 participates in the signalling, regulating the voltage-gated K(+) channel KCNA3. |
