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WNK4 kinase: from structure to physiology.
Murillo-de-Ozores, Adrián Rafael; Rodríguez-Gama, Alejandro; Carbajal-Contreras, Héctor; Gamba, Gerardo; Castañeda-Bueno, María.
Afiliação
  • Murillo-de-Ozores AR; Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
  • Rodríguez-Gama A; Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacan, Mexico City, Mexico.
  • Carbajal-Contreras H; Stowers Institute for Medical Research, Kansas City, Missouri.
  • Gamba G; Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
  • Castañeda-Bueno M; Combined Studies Program in Medicine MD/PhD (PECEM), Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacan, Mexico City, Mexico, Mexico.
Am J Physiol Renal Physiol ; 320(3): F378-F403, 2021 03 01.
Article em En | MEDLINE | ID: mdl-33491560
With no lysine kinase-4 (WNK4) belongs to a serine-threonine kinase family characterized by the atypical positioning of its catalytic lysine. Despite the fact that WNK4 has been found in many tissues, the majority of its study has revolved around its function in the kidney, specifically as a positive regulator of the thiazide-sensitive NaCl cotransporter (NCC) in the distal convoluted tubule of the nephron. This is explained by the description of gain-of-function mutations in the gene encoding WNK4 that causes familial hyperkalemic hypertension. This disease is mainly driven by increased downstream activation of the Ste20/SPS1-related proline-alanine-rich kinase/oxidative stress responsive kinase-1-NCC pathway, which increases salt reabsorption in the distal convoluted tubule and indirectly impairs renal K+ secretion. Here, we review the large volume of information that has accumulated about different aspects of WNK4 function. We first review the knowledge on WNK4 structure and enumerate the functional domains and motifs that have been characterized. Then, we discuss WNK4 physiological functions based on the information obtained from in vitro studies and from a diverse set of genetically modified mouse models with altered WNK4 function. We then review in vitro and in vivo evidence on the different levels of regulation of WNK4. Finally, we go through the evidence that has suggested how different physiological conditions act through WNK4 to modulate NCC activity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Potássio / Receptores de Droga / Proteínas Serina-Treonina Quinases / Simportadores de Cloreto de Sódio / Néfrons Limite: Animals / Humans Idioma: En Revista: Am J Physiol Renal Physiol Assunto da revista: FISIOLOGIA / NEFROLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Potássio / Receptores de Droga / Proteínas Serina-Treonina Quinases / Simportadores de Cloreto de Sódio / Néfrons Limite: Animals / Humans Idioma: En Revista: Am J Physiol Renal Physiol Assunto da revista: FISIOLOGIA / NEFROLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos