A regulated NH2-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 NH2-terminal Sgk1 variant with enhanced function is expressed in the collecting duct

Journal article

Open access

Peer reviewed

A regulated NH2-terminal Sgk1 variant with enhanced function is expressed in the collecting duct

Nandita S Raikwar, Kang Z Liu and Christie P Thomas

American journal of physiology. Renal physiology, Vol.303(11), pp.F1527-1533

12/01/2012

DOI: 10.1152/ajprenal.00191.2012

PMCID: PMC3532487

PMID: 23034940

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Abstract

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.

Cell Line

Kidney Tubules, Collecting - physiology

Immediate-Early Proteins - physiology

Insulin - physiology

Protein-Serine-Threonine Kinases - physiology

Humans

Rats, Inbred F344

Aldosterone - physiology

Protein-Serine-Threonine Kinases - genetics

Rats

Sodium - metabolism

Kidney Tubules, Collecting - cytology

Protein Isoforms - physiology

Thyroid Gland - physiology

Animals

Immediate-Early Proteins - genetics

HEK293 Cells

Models, Animal

Biological Transport - physiology

Genetic Variation - genetics

Mice

Epithelial Sodium Channels - physiology

Thyroid Gland - cytology

Details

Title: Subtitle: A regulated NH2-terminal Sgk1 variant with enhanced function is expressed in the collecting duct
Creators: Nandita S Raikwar - Dept. of Internal Medicine, Univ. of Iowa, Iowa City, IA 52242, USA
Kang Z Liu
Christie P Thomas
Resource Type: Journal article
Publication Details: American journal of physiology. Renal physiology, Vol.303(11), pp.F1527-1533
DOI: 10.1152/ajprenal.00191.2012
PMID: 23034940
PMCID: PMC3532487
NLM abbreviation: Am J Physiol Renal Physiol
ISSN: 0363-6127
eISSN: 1522-1466
Publisher: United States
Grant note: HL71664 / NHLBI NIH HHS DK090053 / NIDDK NIH HHS R01 DK090053 / NIDDK NIH HHS R01 HL071664 / NHLBI NIH HHS
Language: English
Date published: 12/01/2012
Academic Unit: Stead Family Department of Pediatrics; Obstetrics and Gynecology; Internal Medicine
Record Identifier: 9983985904402771

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