2024-03-28T08:36:20Zhttp://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/292092022-06-28T11:42:44Zcom_10324_32522com_10324_952com_10324_894com_10324_43677com_10324_954com_10324_1134com_10324_931col_10324_32523col_10324_43678col_10324_1213
Molecular Determinants of Kv1.3 Potassium Channels-induced Proliferation
Jiménez Pérez, Laura
Cidad Velasco, María del Pilar
Álvarez Miguel, Inés
Santos Hipólito, Alba
Torres Merino, Rebeca
Alonso Alonso, Esperanza
Fuente García, Miguel Ángel de la
Pérez García, María Teresa
López López, José Ramón
Potasio
Células
Producción Científica
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.
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.
2018-03-26T10:31:02Z
2018-03-26T10:31:02Z
2016
info:eu-repo/semantics/article
https://doi.org/10.1074/jbc.M115.678995
The journal of biological chemistry, Febrero 2016, vol. 291, n. 7, p. 3569-3580
0021-9258
http://uvadoc.uva.es/handle/10324/29209
3569
7
3580
The journal of biological chemistry
291
eng
http://www.jbc.org/content/291/7/3569.full
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Society for Biochemistry and Molecular Biology