WNK Kinase Signaling in Ion Homeostasis and Human Disease

Masoud Shekarabi; Jinwei Zhang; Arjun R Khanna; David H Ellison; Eric Delpire; Kristopher T Kahle

doi:10.1016/j.cmet.2017.01.007

WNK Kinase Signaling in Ion Homeostasis and Human Disease

Cell Metab. 2017 Feb 7;25(2):285-299. doi: 10.1016/j.cmet.2017.01.007.

Authors

Masoud Shekarabi¹, Jinwei Zhang², Arjun R Khanna³, David H Ellison⁴, Eric Delpire⁵, Kristopher T Kahle⁶

Affiliations

¹ Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
² Departments of Neurosurgery, Centers for Mendelian Genomics, Yale School of Medicine, New Haven, CT 06477, USA; MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
³ Department of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurosurgery, Harvard Medical School, Boston, MA 02115, USA.
⁴ Division of Nephrology & Hypertension, Department of Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA; VA Portland Health Care System, Portland, OR 97239, USA.
⁵ Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
⁶ Departments of Neurosurgery, Pediatrics, and Cellular & Molecular Physiology, Centers for Mendelian Genomics, Yale School of Medicine, New Haven, CT 06477, USA. Electronic address: kristopher.kahle@yale.edu.

PMID: 28178566
DOI: 10.1016/j.cmet.2017.01.007

Abstract

WNK kinases, along with their upstream regulators (CUL3/KLHL3) and downstream targets (the SPAK/OSR1 kinases and the cation-Cl^- cotransporters [CCCs]), comprise a signaling cascade essential for ion homeostasis in the kidney and nervous system. Recent work has furthered our understanding of the WNKs in epithelial transport, cell volume homeostasis, and GABA signaling, and uncovered novel roles for this pathway in immune cell function and cell proliferation.

Keywords: GABA; KCC2; KCC3; NCC; NKCC1; WNK1; WNK3; WNK4; chloride; homeostasis; kidney.

Publication types

Review

MeSH terms

Amino Acid Sequence
Animals
Biological Transport
Cell Size
Disease*
Homeostasis*
Humans
Ions
Protein Serine-Threonine Kinases / metabolism*
Signal Transduction*

Substances

Ions
Protein Serine-Threonine Kinases

Grants and funding

I01 BX002228/BX/BLRD VA/United States