Disease relevance of WNK3

• WNK3 lies within the critical linkage interval for several human monogenic disorders, including X-linked mental retardation [1].
• WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1) [2].
• In contrast, WNK3 had no effect on the activity of the cardiac long-QT syndrome K+ channel KCNQ1/KCNE1 when co-expressed in oocytes [2].

High impact information on WNK3

• Here, we show that WNK3 completely prevents the cell swelling-induced activation of KCC1-KCC4 in Xenopus oocytes [3].
• Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway [4].
• Suppression of endogenous WNK3 protein by RNA interference accelerates the apoptotic response and promotes the activation of caspase-3 [4].
• Endogenous WNK3 protein is an active protein kinase when immunoprecipitated from cells and its overexpression increases the survival of HeLa cells by delaying the onset of apoptosis [4].
• However, additional co-expression studies in oocytes revealed WNK3 inhibited the renal-specific K+ channel ROMK1 activity greater than 5.5-fold (p < .0001) by altering its plasmalemmal surface expression; WNK3 did not affect ROMK1's conductance or open/closed probability [2].

Biological context of WNK3

• The WNK3 transcript has an open reading frame of 5403 nucleotides and encodes a putative protein of 1800 amino acids [1].
• The WNK3 transcript is expressed in several human fetal and adult tissues and has at least two splice isoforms generated by the alternative splicing of exon 18 and exon 22 which maintain the open reading frame [1].
• The human WNK3 gene comprises 24 exons and lies within a 559 kb genomic segment on chromosome Xp11.22 which has conserved synteny with a 705 kb genomic segment of human chromosome 9q22.31 which contains WNK2 [1].

Associations of WNK3 with chemical compounds

• WNK3 did not alter paracellular Cl- flux in tetracycline-responsive MDCK II cells, nor affect amiloride-sensitive currents when co-expressed with ENaC in Xenopus laevis oocytes [2].

Other interactions of WNK3

• The predicted WNK3 protein has a similar structural organization to the other human WNK kinases [1].

References