WNK kinases regulate sodium chloride and potassium transport by the aldosterone-sensitive distal nephron.
With-No-Lysine [K] (WNKs) are a recently discovered family of serine/threonine protein kinases that contain a uniquely structured catalytic domain. Mutations in the genes encoding two family members, WNK1 and WNK4, cause a chloride-dependent, thiazide-sensitive inherited syndrome of hypertension and hyperkalemia. Over the past 5 years, physiologic studies have demonstrated that these proteins regulate transcellular and paracellular epithelial ion flux. In this mini review, we discuss WNK1 and WNK4 gene products and their regulatory effects on sodium chloride and potassium handling in the aldosterone-sensitive distal nephron. Experimental observations regarding the effects of these proteins on transport processes mediated by the thiazide-sensitive Na-Cl co-transporter, the epithelial sodium channel, the renal outer medullary potassium channel, and the paracellular pathway integrate into a model that suggests an essential role for WNKs in coordinating renal Na-Cl reabsorption and K(+) secretion.
Subramanya
A R
AR
Department of Medicine, Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, Oregon 97239, USA.
Yang
C-L
CL
McCormick
J A
JA
Ellison
D H
DH
D000450:Aldosterone / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006977:Hypertension, Renal / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D009399:Nephrons / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012965:Sodium Chloride / Q000378:metabolism*; D000076204:WNK Lysine-Deficient Protein Kinase 1
D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D012965:Sodium Chloride; D000450:Aldosterone; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human; C433806:WNK4 protein, human; D011188:Potassium