Mechanism of regulation of renal ion transport by WNK kinases

Chou-Long Huang; Sung-Sen Yang; Shih-Hua Lin

doi:10.1097/MNH.0b013e32830dd580

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Mechanism of regulation of renal ion transport by WNK kinases

Journal article

Peer reviewed

Mechanism of regulation of renal ion transport by WNK kinases

Chou-Long Huang, Sung-Sen Yang and Shih-Hua Lin

Current opinion in nephrology and hypertension, Vol.17(5), pp.519-525

09/2008

DOI: 10.1097/MNH.0b013e32830dd580

PMID: 18695394

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Abstract

This review summarizes recent advances in the understanding of the mechanism of regulation of renal ion transport by WNK kinases. There are four mammalian WNK [with-no-lysine (K)] kinases: WNK1-WNK4. Mutations of WNK1 and WNK4 in humans cause hypertension and hyperkalemia at least partly by altering renal sodium and potassium transport. WNK1 and WNK4 stimulate endocytosis of ROMK1 by recruiting an endocytic scaffold protein, intersectin. The recruitment is independent of the kinase activity and occurs between the PXXP motif of WNKs and the SH3 domain of intersectin. Regulation of cation-chloride-coupled cotransporters, Na+-K+-2Cl(-) cotransporter (NKCC) 1 and NKCC2 [and the Na-Cl co-transporter (NCC), under some conditions] by WNKs requires kinase activity. WNK1 and WNK4 bind with and phosphorylate two Ste20-related protein kinases, OSR1 and SPAK, which in turn bind with and phosphorylate NKCCs and NCC to increase their activity. Binding of OSR1/SPAK to upstream activators (WNKs) and downstream substrates (NKCCs and NCC) are both mediated by a docking site in the C-terminus of OSR1/SPAK and RFX[V/I] motifs present in WNKs or in NKCCs and NCC. WNKs regulate ion transport via both catalytic and noncatalytic mechanisms. We discuss hypotheses that WNKs, contrasting with aldosterone, play important roles in dissociating sodium reabsorption from potassium secretion.

Animals

Humans

Intracellular Signaling Peptides and Proteins

Ion Transport

Kidney - metabolism

Minor Histocompatibility Antigens

Potassium - metabolism

Protein-Serine-Threonine Kinases - physiology

Pseudohypoaldosteronism - physiopathology

Sodium - metabolism

WNK Lysine-Deficient Protein Kinase 1

Details

Title: Subtitle: Mechanism of regulation of renal ion transport by WNK kinases
Creators: Chou-Long Huang - Southwestern Medical Center
Sung-Sen Yang - National Defense Medical Center
Shih-Hua Lin - National Defense Medical Center
Resource Type: Journal article
Publication Details: Current opinion in nephrology and hypertension, Vol.17(5), pp.519-525
DOI: 10.1097/MNH.0b013e32830dd580
PMID: 18695394
ISSN: 1062-4821
eISSN: 1473-6543
Grant note: DK-59530 / NIDDK NIH HHS
Language: English
Date published: 09/2008
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984359787102771

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