Journal article
Serum and Glucocorticoid-induced Kinase (SGK) 1 and the Epithelial Sodium Channel Are Regulated by Multiple with No Lysine (WNK) Family Members
The Journal of biological chemistry, Vol.285(33), pp.25161-25167
08/13/2010
DOI: 10.1074/jbc.M110.103432
PMCID: PMC2919078
PMID: 20525693
Abstract
The four WNK (with no lysine (K)) protein kinases affect ion balance and contain an unusual protein kinase domain due to the unique placement of the active site lysine. Mutations in two WNKs cause a heritable form of ion imbalance culminating in hypertension. WNK1 activates the serum- and glucocorticoid-induced protein kinase SGK1; the mechanism is noncatalytic. SGK1 increases membrane expression of the epithelial sodium channel (ENaC) and sodium reabsorption via phosphorylation and sequestering of the E3 ubiquitin ligase neural precursor cell expressed, developmentally down-regulated 4-2 (Nedd4-2), which otherwise promotes ENaC endocytosis. Questions remain about the intrinsic abilities of WNK family members to regulate this pathway. We find that expression of the N termini of all four WNKs results in modest to strong activation of SGK1. In reconstitution experiments in the same cell line all four WNKs also increase sodium current blocked by the ENaC inhibitor amiloride. The N termini of the WNKs also have the capacity to interact with SGK1. More detailed analysis of activation by WNK4 suggests mechanisms in common with WNK1. Further evidence for the importance of WNK1 in this process comes from the ability of Nedd4-2 to bind to WNK1 and the finding that endogenous SGK1 has reduced activity if WNK1 is knocked down by small interfering RNA.
Details
- Title: Subtitle
- Serum and Glucocorticoid-induced Kinase (SGK) 1 and the Epithelial Sodium Channel Are Regulated by Multiple with No Lysine (WNK) Family Members
- Creators
- Charles J. Heise - The University of Texas Southwestern Medical CenterBing-e Xu - The University of Texas Southwestern Medical CenterStaci L. Deaton - The University of Texas Southwestern Medical CenterSeung-Kuy Cha - The University of Texas Southwestern Medical CenterChih-Jen Cheng - The University of Texas Southwestern Medical CenterSvetlana Earnest - The University of Texas Southwestern Medical CenterSamarpita Sengupta - The University of Texas Southwestern Medical CenterYu-Chi Juang - The University of Texas Southwestern Medical CenterSteve Stippec - The University of Texas Southwestern Medical CenterYingda Xu - The University of Texas Southwestern Medical CenterYingming Zhao - The University of Texas Southwestern Medical CenterChou-Long Huang - The University of Texas Southwestern Medical CenterMelanie H. Cobb - The University of Texas Southwestern Medical Center
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.285(33), pp.25161-25167
- DOI
- 10.1074/jbc.M110.103432
- PMID
- 20525693
- PMCID
- PMC2919078
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 08/13/2010
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359697602771
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