Annals of neurosciences
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Annals of neurosciences · Apr 2011
ReviewEmerging role of WNK1 in pathologic central nervous system signaling.
WNK1 (with no lysine (K)) is a widely expressed serine/threonine protein kinase. The role of this kinase was first described in the kidney where it dynamically controls ion channels that regulate changes in cell volume. WNK1, through intermediates oxidative stress-responsive kinase-1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK), phosphorylates the inwardly directed Na(+)-K+-Cl(-)--cotransporter 1 (NKCC1) and the outwardly directed K(+)-Cl(-)-cotransporter 2 (KCC2), activating and deactivating these channels, respectively. ⋯ Growing evidence implicates WNK1 playing a critical role in pathologic nervous system signaling where changes in intracellular ion concentration in response to γ-aminobutyric-acid (GABA) can activate otherwise silent pathways. This review will focus on current research about WNK1, its downstream effectors and role in GABA signaling. Future perspectives include investigating WNK1 expression in the CNS after spinal cord injury (SCI), where altered neuronal signaling could underlie pathological states such as neuropathic pain (NP).