A regulated N[H.sub.2]-terminal Sgk1 variant with enhanced function is expressed in the collecting duct

Nandita S Raikwar; Kang Z Liu; Christie P Thomas

doi:10.1152/ajprenal.00191.2012.

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A regulated N[H.sub.2]-terminal Sgk1 variant with enhanced function is expressed in the collecting duct

Abstract

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A regulated N[H.sub.2]-terminal Sgk1 variant with enhanced function is expressed in the collecting duct

Nandita S Raikwar, Kang Z Liu and Christie P Thomas

The American journal of physiology, Vol.303(6), p.F1527

12/01/2012

DOI: 10.1152/ajprenal.00191.2012.

PMCID: PMC3532487

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Abstract

Sgk1 is a relatively unstable kinase that regulates epithelial [Na.sup.+] 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 N[H.sub.2]-terminal variant Sgkl isoform, Sgk1_i3. Sgk1_i3 contains a polybasic motif, KKR, in its N[H.sub.2] terminus that regulates ubiquitination and stability of the expressed protein in HEK293 cells. In Fisher rat thyroid, and [mpkCCD.sub.c14] cells, Sgk1_i3 had a significantly greater effect on [Na.sup.+] transport compared with Sgk1 and its stimulatory effect was dependent on the kinase domain. Sgk1_i3 increased the abundance of cleaved epithelial [Na.sup.+] 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. aldosterone; [Na.sup.+] transport; epithelial [Na.sup.+] channel doi: 10.1152/ajprenal.00191.2012.

Gene Expression

Insulin

Aldosterone

Genetic aspects

Genetic transcription

Genetic variation

Physiological aspects

Details

Title: Subtitle: A regulated N[H.sub.2]-terminal Sgk1 variant with enhanced function is expressed in the collecting duct
Creators: Nandita S Raikwar
Kang Z Liu
Christie P Thomas
Resource Type: Abstract
Publication Details: The American journal of physiology, Vol.303(6), p.F1527
Publisher: American Physiological Society
DOI: 10.1152/ajprenal.00191.2012.
PMCID: PMC3532487
ISSN: 0002-9513
eISSN: 2163-5773
Language: English
Date published: 12/01/2012
Description audience: Academic
Academic Unit: Obstetrics and Gynecology; Internal Medicine; Nephrology; Stead Family Department of Pediatrics
Record Identifier: 9984363283802771

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