C-terminally truncated, kidney-specific variants of the WNK4 kinase lack several sites that regulate its activity.

ABSTRACT: WNK lysine-deficient protein kinase 4 (WNK4) is an important regulator of renal salt handling. Mutations in its gene cause pseudohypoaldosteronism type II, mainly arising from overactivation of the renal Na⁺/Cl^- cotransporter (NCC). In addition to full-length WNK4, we have observed faster migrating bands (between 95 and 130 kDa) in Western blots of kidney lysates. Therefore, we hypothesized that these could correspond to uncharacterized WNK4 variants. Here, using several WNK4 antibodies and WNK4^-/- mice as controls, we showed that these bands indeed correspond to short WNK4 variants that are not observed in other tissue lysates. LC-MS/MS confirmed these bands as WNK4 variants that lack C-terminal segments. In HEK293 cells, truncation of WNK4's C terminus at

SUBMITTER: Murillo-de-Ozores AR 

PROVIDER: S-EPMC6078442 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature