WNK Kinases, Renal Ion Transport and Hypertension

Vol. 28, No. 5, 2008

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Kidney and beyond - Review Article

WNK Kinases, Renal Ion Transport and Hypertension
Pedro San-Cristobal^a, Paola de los Heros^a, José Ponce-Coria^a, Erika Moreno^{a, b}, Gerardo Gamba^a

^aMolecular Physiology Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán and Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, and
^bUniversidad Autónoma del Estado de Hidalgo, Pachuca, México

Address of Corresponding Author

Am J Nephrol 2008;28:860-870 (DOI: 10.1159/000139639)

Key Words

Diuretics
Distal convoluted tubule
Salt transport
Potassium excretion
Phosphorylation

Abstract

Two members of a recently discovered family of protein kinases are the cause of an inherited disease known as pseudohypoaldosteronism type II (PHAII). These patients exhibit arterial hypertension together with hyperkalemia and metabolic acidosis. This is a mirror image of Gitelman disease that is due to inactivating mutations of the SLC12A3 gene that encodes the thiazide-sensitive Na⁺:Cl^- cotransporter. The uncovered genes causing PHAII encode for serine/threonine kinases known as WNK1 and WNK4. Physiological and biochemical studies have revealed that WNK1 and WNK4 modulate the activity of several transport pathways of the aldosterone-sensitive distal nephron, thus increasing our understanding of how diverse renal ion transport proteins are coordinated to regulate normal blood pressure levels. Observations discussed in the present work place WNK1 and WNK4 as genes involved in the genesis of essential hypertension and as potential targets for the development of antihypertensive drugs.

Author Contacts

Gerardo Gamba, MD, PhD
Molecular Physiology Unit, Vasco de Quiroga No. 15
Tlalpan 14000, México City (México)
Tel. +52 55 5513 3868, Fax +52 55 5655 0382
E-Mail gamba@biomedicas.unam.mx or gamba@quetzal.innsz.mx

Article Information

Received: March 10, 2008
Accepted: March 31, 2008
Published online: June 12, 2008
Number of Print Pages : 11
Number of Figures : 2, Number of Tables : 2, Number of References : 68

Medline Abstract (ID 18547946)

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