Por favor, use este identificador para citar o enlazar este ítem:http://uvadoc.uva.es/handle/10324/29209
Molecular Determinants of Kv1.3 Potassium Channels-induced Proliferation
Año del Documento
American Society for Biochemistry and Molecular Biology
The journal of biological chemistry, Febrero 2016, vol. 291, n. 7, p. 3569-3580
Changes in voltage-dependent potassium channels (Kv channels) associate to proliferation in many cell types, including transfected HEK293 cells. In this system Kv1.5 overexpression decreases proliferation, whereas Kv1.3 expression increases it independently of K+ fluxes. To identify Kv1.3 domains involved in a proliferation-associated signaling mechanism(s), we constructed chimeric Kv1.3-Kv1.5 channels and point-mutant Kv1.3 channels, which were expressed as GFP- or cherry-fusion proteins. We studied their trafficking and functional expression, combining immunocytochemical and electrophysiological methods, and their impact on cell proliferation. We found that the C terminus is necessary for Kv1.3-induced proliferation. We distinguished two residues (Tyr-447 and Ser-459) whose mutation to alanine abolished proliferation. The insertion into Kv1.5 of a sequence comprising these two residues increased proliferation rate. Moreover, Kv1.3 voltage-dependent transitions from closed to open conformation induced MEK-ERK1/2-dependent Tyr-447 phosphorylation. We conclude that the mechanisms for Kv1.3-induced proliferation involve the accessibility of key docking sites at the C terminus. For one of these sites (Tyr-447) we demonstrated the contribution of MEK/ERK-dependent phosphorylation, which is regulated by voltage-induced conformational changes.
Revisión por pares
Ministerio de Economía y Competitividad (MINECO), Instituto de Salud Carlos III y Programa Estatal de Investigación , Fundación Ramón Areces y Consejería de Sanidad de la Junta de Castilla y León.
Version del Editor
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International