WNK kinases, including WNK3, and the associated downstream Ste20/SPS1-related proline-alanine-rich protein kinase (SPAK) and oxidative stress responsive 1 (OSR1) kinases, comprise an important signaling cascade that regulates the cation-chloride cotransporters. Ischemia-induced stimulation of the bumetanide-sensitive Na(+)-K(+)-Cl(-) cotransporter (NKCC1) plays an important role in the pathophysiology of experimental stroke, but the mechanism of its regulation in this context is unknown.
Data identify a novel role for the WNK3-SPAK/OSR1-NKCC1 signaling pathway in ischemic neuroglial injury and suggest the WNK3-SPAK/OSR1 kinase pathway as a therapeutic target for neuroprotection after ischemic stroke 1).
1)
Begum G, Yuan H, Kahle KT, Li L, Wang S, Shi Y, Shmukler BE, Yang SS, Lin SH,
Alper SL, Sun D. Inhibition of WNK3 Kinase Signaling Reduces Brain Damage and
Accelerates Neurological Recovery After Stroke. Stroke. 2015 Jul;46(7):1956-65.
doi: 10.1161/STROKEAHA.115.008939. PubMed PMID: 26069258; PubMed Central PMCID:
PMC4643659.