Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation ( ). The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, regulating their activity (By similarity). Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively . Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5 . Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression (, ). Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1 (, ). WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity (, ).
Subcellular locations: Cytoplasm, Cell membrane
Expressed in various cancer cell lines (at protein level). Predominantly expressed in heart, brain, skeletal muscle and colon.