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Role of SPAK in Mediating Regulation of NCC in the Kidney in Response to Low K Diet
Author(s) -
Liu Jie,
Coleman Richard A.,
Grimm P. Richard,
Delpire Eric,
Welling Paul A.,
Wade James B.
Publication year - 2012
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.26.1_supplement.867.36
Subject(s) - phosphorylation , western blot , kinase , cotransporter , endocrinology , medicine , chemistry , alanine , biology , microbiology and biotechnology , biochemistry , sodium , gene , amino acid , organic chemistry
The NaCl cotransporter (NCC) is stimulated by low K diet by an unknown mechanism. Since recent work has shown that the STE20/SPS‐1‐related proline‐alanine‐rich protein kinase (SPAK) can function to stimulate NCC by phosphorylation of specific N‐terminal sites, we investigated if the NCC response to low K diet is mediated by SPAK. Using phospho‐specific antibodies in Western blot and immunolocalization studies of WT and SPAK −/− mice fed a low K or control diet for 4 days, we found that Low K diet more than doubled total NCC expression and phosphorylation of NCC at the T58 site. This was associated with an increase in total SPAK expression in cortical homogenates and an increase in phosphorylation of SPAK at the T383 activation site. Changes in NCC, pNCC and pSPAK in response to low K diet were absent in SPAK knock‐out mice. These findings show that SPAK is a critical mediator of increased NCC expression and activation by phosphorylation in the DCT in response to low K diet. Supported by grants from the National Institutes of Health (1RC1DK086817 to PAW, DK32839 to JBW, GM074771 to ED and 5T32HL072751 to PRG).