Document Detail


A regulated NH2-terminal Sgk1 variant with enhanced function is expressed in the collecting duct.
MedLine Citation:
PMID:  23034940     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sgk1 is a relatively unstable kinase that regulates epithelial Na(+) transport in the distal nephron of the kidney. We identified a 5' variant alternate transcript of human Sgk1 (Sgk1_v3) that is expressed in the connecting tubule and collecting duct, is regulated by aldosterone and insulin, and is predicted to encode an NH(2)-terminal variant Sgk1 isoform, Sgk1_i3. Sgk1_i3 contains a polybasic motif, KKR, in its NH(2) terminus that regulates ubiquitination and stability of the expressed protein in HEK293 cells. In Fisher rat thyroid, and mpkCCD(c14) cells, Sgk1_i3 had a significantly greater effect on Na(+) transport compared with Sgk1 and its stimulatory effect was dependent on the kinase domain. Sgk1_i3 increased the abundance of cleaved epithelial Na(+) channel (ENaC) subunits at the cell surface, which was inhibited by coexpression of Nedd4-2. Together, the data demonstrate that a renally expressed Sgk1 isoform, Sgk1_i3, shows improved stability, is regulated by insulin and aldosterone, and stimulates ENaC activity when heterologously expressed in collecting duct cells.
Authors:
Nandita S Raikwar; Kang Z Liu; Christie P Thomas
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2012-10-03
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  303     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-03     Completed Date:  2013-04-02     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F1527-33     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aldosterone / physiology
Animals
Biological Transport / physiology
Cell Line
Epithelial Sodium Channels / physiology
Genetic Variation / genetics*
HEK293 Cells
Humans
Immediate-Early Proteins / genetics*,  physiology*
Insulin / physiology
Kidney Tubules, Collecting / cytology,  physiology*
Mice
Models, Animal
Protein Isoforms / physiology
Protein-Serine-Threonine Kinases / genetics*,  physiology*
Rats
Rats, Inbred F344
Sodium / metabolism
Thyroid Gland / cytology,  physiology
Grant Support
ID/Acronym/Agency:
DK090053/DK/NIDDK NIH HHS; HL71664/HL/NHLBI NIH HHS; R01 DK090053/DK/NIDDK NIH HHS; R01 HL071664/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Epithelial Sodium Channels; 0/Immediate-Early Proteins; 0/Insulin; 0/Protein Isoforms; 4964P6T9RB/Aldosterone; 9NEZ333N27/Sodium; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/serum-glucocorticoid regulated kinase
Comments/Corrections

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