WNK1 Antibody

The WNK [with no lysine (K)] family of serine/threonine kinases is characterized by having a cysteine in place of lysine in subdomain II of its kinase activation domain (1,2). The lysine necessary for phosphoryl transfer is located in an atypical position in the catalytic domain. Four WNK family members have been identified in humans (WNK1-4) and have been implicated in regulating ion permeability (3). Mutations in the WNK1 and WNK4 genes in humans cause pseudohypoaldosteronism type II (PHAII), an autosomal dominant disorder leading to hypertension, hyperkalemia, and renal tubular acidosis (4). WNK4 is specifically expressed in the kidney, whereas WNK1 has a wider distribution but is predominantly expressed in polarized epithelia (1-3). Heterozygous Wnk1 mutations in mice result in a significant decrease in blood pressure, while homozygous mutations are embryonic lethal (5). WNK1 is phosphorylated by Akt at Thr60 (6). In addition, WNK1 may be autophosphorylated at Ser382 in the activation loop, which is thought to be required for its kinase activity (7). 1.Veríssimo, F. and Jordan, P. (2001) Oncogene 20, 5562-9. 2.Xu, B. et al. (2000) J Biol Chem 275, 16795-801. 3.Choate, K.A. et al. (2003) Proc Natl Acad Sci USA 100, 663-8. 4.Wilson, F.H. et al. (2001) Science 293, 1107-12. 5.Zambrowicz, B.P. et al. (2003) Proc Natl Acad Sci USA 100, 14109-14. 6.Vitari, A.C. et al. (2004) Biochem J 378, 257-68. 7.Xu, B.E. et al. (2002) J Biol Chem 277, 48456-62.