Premium
WNK4 inhibits NCC protein expression through MAPK ERK1/2 signaling pathway independent of SPAK/OSR1 pathway
Author(s) -
Feng Xiuyan,
Zhang Yiqian,
Wang Yanhui,
Zhou Bo,
Wang Dexuan,
Zhang Xuemei,
Gu Dingying,
Cai Hui
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1041.47
Subject(s) - mapk/erk pathway , kinase , chemistry , microbiology and biotechnology , signal transduction , protein kinase a , cancer research , biochemistry , biology
WNK kinase is a subfamily of serine/threonine kinases. WNK1 and WNK4 were shown to stimulate NCC activity through SPAK and OSR1 phosphorylation at T46, T55, T60, S73 and S91. We previously showed that WNK4 phosphorylates ERK1/2 and knocking down WNK4 expression increases NCC expressions. We also found that knock‐down WNK4 expression significantly reduced ERK1/2 phosphorylation and knock down ERK1/2 expression increased total and surface NCC expressions. To discrete the phosphorylation sites of SPAK/OSR1 from ERK1/2 in WNK4¡s effect on NCC, we mutated these putative SPAK phosphorylation sites of NCC to determine the effects of WNK4 on NCC protein expressions. When Cos‐7 cells were transfected with single mutation of NCC T46A, T50A, T60 or S73A, WNK4 still inhibits NCC protein expression whereas Cos‐7 cells were trasnfected with single mutation of either NCC T55A or S91A, WNK4 lose its inhibitory effect on NCC protein expression. These data suggest that WNK4 inhibits NCC protein expression through a MAPK ERK1/2 signaling pathway using the discrete phosphorylation sites of NCC independent of SPAK/OSR1 pathway.