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Expression, function and regulation of NH2‐terminal Sgk1 variants
Author(s) -
Raikwar Nandita S,
Kelley Elizabeth A,
Snyder Peter M,
Thomas Christie P
Publication year - 2009
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.23.1_supplement.998.5
Subject(s) - sgk1 , epithelial sodium channel , gene isoform , kinase , biology , microbiology and biotechnology , chemistry , gene , sodium , biochemistry , organic chemistry
Sgk1 is an aldosterone induced kinase that regulates epithelial sodium channel (ENaC)‐mediated Na+ transport. We identified N‐terminal variant Sgk1 isoforms: Sgk1_i2 and Sgk1_i3 that arise by alternate transcription initiation from human Sgk1 transcripts, Sgk1_v2 and Sgk1_v3 respectively. These isoforms are more resistant to proteosomal degradation as compared to Sgk1. Furthermore, aldosterone stimulates Sgk1_v3 mRNA expression in a collecting duct cell line, mpkCCDc14, indicating that this 5' variant may have a role in mineralocorticoid‐regulated Na+ reabsorption. When expressed together with ENaC subunits in FRT epithelia, Sgk1_i2 or Sgk1_i3 stimulate amiloride‐sensitive Na+ transport an effect that appears to be mediated via the kinase domain of Sgk1. Collectively, the data demonstrate that N‐terminal variants of Sgk1 are more stable, functionally more active and are expressed and regulated in collecting duct epithelia raising the possibility that these variants may have a physiological role. NHLBI and VA Merit