WNK2
Description
The WNK2 (WNK lysine deficient protein kinase 2) is a protein-coding gene located on chromosome 9.
Serine/threonine-protein kinase WNK2 is an enzyme that in humans is encoded by the WNK2 gene. The protein encoded by this gene is a cytoplasmic serine-threonine kinase that contains cysteine in place of the lysine found at the conserved ATP-binding location in subdomain II of protein kinases. Since this protein does have kinase activity, it is possible that another lysine in the kinase subdomain I can substitute for the missing conserved lysine.
The WNK2 gene encodes a serine/threonine-protein kinase that plays a crucial role in the WNK2-SPAK/OSR1 kinase cascade, which regulates electrolyte homeostasis, cell signaling, survival, and proliferation. WNK2 directly activates downstream kinases OXSR1/OSR1 and STK39/SPAK, leading to the phosphorylation of ion cotransporters, ultimately modulating their activity. Notably, WNK2 acts as both an activator of sodium-coupled chloride cotransporters (SLC12A2, SCNN1A, SCNN1B, SCNN1D, and SGK1) and an inhibitor of potassium-coupled chloride cotransporters (SLC12A5). Furthermore, WNK2 negatively regulates the EGF-induced activation of the ERK/MAPK pathway and subsequent cell cycle progression. This regulation is achieved by influencing the activity of MAP2K1, a key player in the MAPK pathway. WNK2 modulates MAP2K1 activity through its interaction with PAK1, a kinase that phosphorylates MAP2K1. WNK2's control over PAK1 is mediated by its influence on the balance of activity between RHOA and RAC1, two upstream regulators of PAK1. WNK2 forms a complex with the phosphorylated form of STK39.
WNK2 is also known as NY-CO-43, P/OKcl.13, PRKWNK2, SDCCAG43.
