WNK Kinase (WNK激酶)

WNK kinases are a class of serine/threonine protein kinases with unique structures and functions, belonging to a special kinase family. WNK kinases are characterized by the lack of a commonly conserved lysine in the kinase subdomain II, which is essential for ATP binding in other kinases. The WNK kinase family contains four members in mammals: WNK1, WNK2, WNK3, and WNK4. The main targets of WNK kinases include kinases such as SPAK and OSR1, which are activated by phosphorylation and then regulate the activity of cation-chloride cotransporters (CCCs). CUL3 and KLHL3, as upstream regulators, can regulate the degradation of WNK kinases through ubiquitination. In the kidney, WNK kinases regulate the reabsorption of NaCl and the secretion of K⁺; in terms of cell volume regulation, they can respond to changes in osmotic pressure and adjust ion transport to maintain cell volume stability. In addition, WNK kinases are also involved in the regulation of neuronal GABA signaling, affecting the excitability of neurons. In cancer-related processes, WNK kinases can regulate ion channels, CCCs, etc., and affect the proliferation, migration and invasion of tumor cells. WNK kinases are closely related to a variety of diseases. In hypertension-related diseases, mutations in WNK1 and WNK4 can lead to pseudoaldosteronism type II, causing symptoms such as hypertension and hyperkalemia. In the field of nervous system diseases, abnormalities in WNK kinases are associated with hereditary sensory neuropathy type II, epilepsy, neuropathic pain, and some psychiatric disorders. In cancer, abnormal expression of WNK kinases is associated with the development and prognosis of a variety of cancers, making it a potential target for cancer treatment^{[1][2][3][4][5][6]}.