RT info:eu-repo/semantics/article
T1 Molecular Determinants of Kv1.3 Potassium Channels-induced Proliferation
A1 Jiménez Pérez, Laura
A1 Cidad Velasco, María del Pilar
A1 Álvarez Miguel, Inés
A1 Santos Hipólito, Alba
A1 Torres Merino, Rebeca
A1 Alonso Alonso, Esperanza
A1 Fuente García, Miguel Ángel de la
A1 Pérez García, María Teresa
A1 López López, José Ramón
K1 Potasio
K1 Células
AB 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.
PB American Society for Biochemistry and Molecular Biology
SN 0021-9258
YR 2016
FD 2016
LK http://uvadoc.uva.es/handle/10324/29209
UL http://uvadoc.uva.es/handle/10324/29209
LA eng
NO The journal of biological chemistry, Febrero 2016, vol. 291, n. 7, p. 3569-3580
NO Producción Científica
DS UVaDOC
RD 16-abr-2024