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dc.contributor.authorLeyva Ríos, Karla
dc.contributor.authorPacheco-Alvarez, Diana
dc.identifier.citationMurillo de Ozores, A. R., Rodríguez Gama, A., Bazúa Valenti, S., Leyva Ríos, K., Vázquez N., Pacheco Álvarez, D. … y Castañeda Bueno, M. (2018). C-terminally truncated, kidney-specific variants of the WNK4 kinase lack several sites that regulate its activity. Journal of Biological Chemistry, 293, (31), 12209-12221. DOI: 10.1074/jbc.RA118.003037es_ES, en_US
dc.identifier.issn0021-9258es_ES, en_US
dc.identifier.otherCampus Ciudad de Méxicoes_ES, en_US
dc.description.abstractWNK lysine-deficient protein kinase 4 (WNK4) is an important regulator of renal salt handling. Mutations in its gene cause pseudohypoaldosteronism type II, mainly arising from overac-tivation of the renal Na/Cl cotransporter (NCC). In addition to full-length WNK4, we have observed faster migrating bands (between 95 and 130 kDa) in Western blots of kidney lysates. Therefore, we hypothesized that these could correspond to uncharacterized WNK4 variants. Here, using several WNK4 antibodies and WNK4/ mice as controls, we showed that these bands indeed correspond to short WNK4 variants that are not observed in other tissue lysates. LC-MS/MS confirmed these bands as WNK4 variants that lack C-terminal segments. In HEK293 cells, truncation of WNK4’s C terminus at several positions increased its kinase activity toward Ste20-related proline/ alanine-rich kinase (SPAK), unless the truncated segment included the SPAK-binding site. Of note, this gain-of-function effect was due to the loss of a protein phosphatase 1 (PP1)-bind-ing site in WNK4. Cotransfection with PP1 resulted in WNK4 dephosphorylation, an activity that was abrogated in the PP1-binding site WNK4 mutant. The electrophoretic mobility of the in vivo short variants of renal WNK4 suggested that they lack the SPAK-binding site and thus may not behave as constitutively active kinases toward SPAK. Finally, we show that at least one of the WNK4 short variants may be produced by proteolysis involving a Zn2-dependent metalloprotease, as recombinant full-length WNK4 was cleaved when incubated with kidney lysate. © 2018 American Society for Biochemistry and Molecular Biology Inc. All rights reserved.es_ES, en_US
dc.description.statementofresponsibilityInvestigadoreses_ES, en_US
dc.description.tableofcontentsCiencias de la Saludes_ES, en_US
dc.languageenges_ES, en_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc.es_ES, en_US
dc.relationVersión del autores_ES, en_US
dc.relation.ispartofREPOSITORIO SCRIPTAes_ES, en_US
dc.relation.ispartofOPENAIREes_ES, en_US
dc.rightsAcceso Abiertoes_ES, en_US
dc.rights.uri, en_US
dc.sourceJournal of Biological Chemistry
dc.subjectAmino acidses_ES, en_US
dc.subjectElectrophoretic mobilityes_ES, en_US
dc.subjectC-terminal segmentses_ES, en_US
dc.subjectCo-transfectionses_ES, en_US
dc.subjectConstitutively activeses_ES, en_US
dc.subjectDephosphorylationses_ES, en_US
dc.subjectGain-of functiones_ES, en_US
dc.subjectKinase activityes_ES, en_US
dc.subjectMetallo-proteasees_ES, en_US
dc.subjectProtein phosphatase-1es_ES, en_US
dc.subjectEnzymeses_ES, en_US
dc.subject.classificationMEDICINA Y CIENCIAS DE LA SALUDes_ES, en_US
dc.titleC-terminally truncated, kidney-specific variants of the WNK4 kinase lack several sites that regulate its activityes_ES, en_US
dc.typeArtículoes_ES, en_US
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