Human hypertension caused by mutations in WNK kinases #MMPMID11498583
Wilson FH; Disse-Nicodeme S; Choate KA; Ishikawa K; Nelson-Williams C; Desitter I; Gunel M; Milford DV; Lipkin GW; Achard JM; Feely MP; Dussol B; Berland Y; Unwin RJ; Mayan H; Simon DB; Farfel Z; Jeunemaitre X; Lifton RP
Science 2001[Aug]; 293 (5532): 1107-12 PMID11498583show ga
Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.
Science 2001 ; 293 (5532): 1107-12
