WNK Kinase

The With-No-Lysine (K) (WNK) kinases are a family of serine/threonine kinases, firsted in a screen for novel mitogen-activated protein kinase (MAPK) kinases. Another unique feature of WNKs is their regulation by chloride, which directly binds to the kinase active site and inhibits autophosphorylation and kinase activation. The best-understood function of WNKs is their ability to phosphorylate SPAK and OSR1. Activated SPAK and OSR1 phosphorylate members of the SLC12 family of cation-chloride cotransporters. These include the three related sodium-coupled chloride cotransporters, NCC (sodium chloride cotransporter), and the sodium-potassium-2-chloride cotransporters NKCC1 and NKCC2, as well as the potassium-coupled chloride cotransporters, KCC1–4 (potassium chloride cotransporters). 
Phosphorylation of NCC, NKCC1 and NKCC2 results in transporter activation, whereas phosphorylation of KCCs results in transporter inactivation. Regulation of these transporters by WNKs are important for cell volume control, transepithelial ion transport, and the regulation of intracellular chloride concentration.  In neurons, for example, intracellular chloride concentration determines whether activation of ligand-gated chloride channels, such as the GABAA or glycine receptors, results in a hyperpolarizing or depolarizing effect.


1.Rodan AR,et al. Curr Top Dev Biol. 2017;123:1–47.