WNK1 Protein, Human (sf9, His, GST)

WNK1 is a serine/threonine-protein kinase and a core component of the WNK1-SPAK/OSR1 kinase cascade, which regulates blood pressure and cell volume homeostasis by promoting ion influx. Acting as a molecular crowding sensor, WNK1 detects hyperosmotic stress-induced cell shrinkage and forms membraneless compartments via liquid-liquid phase separation, concentrating itself with substrates OXSR1/OSR1 and STK39/SPAK to facilitate their phosphorylation. Activated OXSR1/OSR1 and STK39/SPAK phosphorylate ion cotransporters (e.g., SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2, SLC12A6/KCC3), enhancing NKCC1/2-mediated ion influx while inhibiting KCC2/3-driven efflux. Beyond ion transport, WNK1 modulates angiogenesis via OXSR1/OSR1 (chemotaxis/invasion) and STK39/SPAK (proliferation). Kinase-independently, WNK1 phosphorylates SYT2 (By similarity), PCF11 (promoting mRNA export), and NEDD4L, and scaffolds membrane transporters (e.g., SLC4A4, TRPV4) to suppress their localization. It also negatively regulates autophagy, participates in mitotic abscission, and may reorganize the actin cytoskeleton. Recent studies reveal WNK1 stabilizes EMC2 as an ER membrane protein complex assembly factor and activates ENaC by recruiting SGK1 to mTORC2 in a kinase-independent manner.