WNK protein kinases modulate cellular Cl- flux by altering the phosphorylation state of the Na-K-Cl and K-Cl cotransporters

Physiology (Bethesda). 2006 Oct:21:326-35. doi: 10.1152/physiol.00015.2006.


Precise control of cellular Cl(-) transport is necessary for many fundamental physiological processes. For example, the intracellular concentration of Cl(-), fine-tuned through the coordinated action of cellular Cl(-) influx and efflux mechanisms, determines whether a neuron's response to GABA is excitatory or inhibitory. In epithelia, synchrony between apical and basolateral Cl(-) flux, and transcellular and paracellular Cl(-) transport, is necessary for efficient transepithelial Cl(-) reabsorption or secretion. In cells throughout the body, coordination of Cl(-) entry and exit mechanisms help defend against changes in cell volume. The Na-K-Cl and K-Cl cotransporters of the SLC12 gene family are important molecular determinants of Cl(-) entry and exit, respectively, in these systems. The WNK serine-threonine kinase family, members of which are mutated in an inherited form of human hypertension, are components of a signaling pathway that coordinates Cl(-) influx and efflux through SLC12 cotransporters to dynamically regulate intracellular Cl(-) activity.

Publication types

  • Review

MeSH terms

  • Biological Transport
  • Chlorine / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • K Cl- Cotransporters
  • Minor Histocompatibility Antigens
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Serine-Threonine Kinases / physiology*
  • Sodium-Potassium-Chloride Symporters / metabolism*
  • Symporters / metabolism*
  • WNK Lysine-Deficient Protein Kinase 1


  • Intracellular Signaling Peptides and Proteins
  • Minor Histocompatibility Antigens
  • Sodium-Potassium-Chloride Symporters
  • Symporters
  • Chlorine
  • Protein Serine-Threonine Kinases
  • WNK Lysine-Deficient Protein Kinase 1
  • WNK1 protein, human
  • WNK4 protein, human