WNK protein kinases modulate cellular Cl- flux by altering the phosphorylation state of the Na-K-Cl and K-Cl cotransporters.
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.
Kahle
Kristopher T
KT
Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Rinehart
Jesse
J
Ring
Aaron
A
Gimenez
Ignacio
I
Gamba
Gerardo
G
Hebert
Steven C
SC
Lifton
Richard P
RP
D001692:Biological Transport; D002713:Chlorine / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D000076204:WNK Lysine-Deficient Protein Kinase 1; D000096922:K Cl- Cotransporters
D002713:Chlorine; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D017346:Protein Serine-Threonine Kinases; D028021:Sodium-Potassium-Chloride Symporters; D027981:Symporters; D000076204:WNK Lysine-Deficient Protein Kinase 1; D000096922:K Cl- Cotransporters; C498743:WNK1 protein, human; C433806:WNK4 protein, human