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WNK-SPAK-NCC cascade revisited: WNK1 stimulates the activity of the Na-Cl cotransporter via SPAK, an effect antagonized by WNK4.
Chávez-Canales, María; Zhang, Chong; Soukaseum, Christelle; Moreno, Erika; Pacheco-Alvarez, Diana; Vidal-Petiot, Emmanuelle; Castañeda-Bueno, María; Vázquez, Norma; Rojas-Vega, Lorena; Meermeier, Nicholas P; Rogers, Shaunessy; Jeunemaitre, Xavier; Yang, Chao-Ling; Ellison, David H; Gamba, Gerardo; Hadchouel, Juliette.
Afiliação
  • Chávez-Canales M; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Zhang C; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Soukaseum C; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Moreno E; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Pacheco-Alvarez D; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Vidal-Petiot E; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Castañeda-Bueno M; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Vázquez N; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Rojas-Vega L; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Meermeier NP; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Rogers S; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Jeunemaitre X; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Yang CL; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Ellison DH; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Gamba G; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
  • Hadchouel J; From the Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, Mexico (M.C.-C., M.C.-B., N.V., L.R.-V., G.G.); Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mex
Hypertension ; 64(5): 1047-53, 2014 Nov.
Article em En | MEDLINE | ID: mdl-25113964
The with-no-lysine (K) kinases, WNK1 and WNK4, are key regulators of blood pressure. Their mutations lead to familial hyperkalemic hypertension (FHHt), associated with an activation of the Na-Cl cotransporter (NCC). Although it is clear that WNK4 mutants activate NCC via Ste20 proline-alanine-rich kinase, the mechanisms responsible for WNK1-related FHHt and alterations in NCC activity are not as clear. We tested whether WNK1 modulates NCC through WNK4, as predicted by some models, by crossing our recently developed WNK1-FHHt mice (WNK1(+/FHHt)) with WNK4(-/-) mice. Surprisingly, the activated NCC, hypertension, and hyperkalemia of WNK1(+/FHHt) mice remain in the absence of WNK4. We demonstrate that WNK1 powerfully stimulates NCC in a WNK4-independent and Ste20 proline-alanine-rich kinase-dependent manner. Moreover, WNK4 decreases the WNK1 and WNK3-mediated activation of NCC. Finally, the formation of oligomers of WNK kinases through their C-terminal coiled-coil domain is essential for their activity toward NCC. In conclusion, WNK kinases form a network in which WNK4 associates with WNK1 and WNK3 to regulate NCC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Proteínas Serina-Treonina Quinases / Simportadores de Cloreto de Sódio Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Hypertension Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Proteínas Serina-Treonina Quinases / Simportadores de Cloreto de Sódio Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Hypertension Ano de publicação: 2014 Tipo de documento: Article