WNK1 and OSR1 regulate the Na + , K + , 2Cl − cotransporter in HeLa cells
- 18 July 2006
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 103 (29), 10883-10888
- https://doi.org/10.1073/pnas.0604607103
Abstract
Oxidative stress-responsive kinase (OSR) 1 and sterile20-related, proline-, alanine-rich kinase (SPAK) are Ste20p-related protein kinases that bind to the sodium, potassium, two chloride cotransporter, NKCC. Here we present evidence that the protein kinase with no lysine [K] (WNK) 1 regulates OSR1, SPAK, and NKCC activities. OSR1 exists in a complex with WNK1 in cells, is activated by recombinant WNK1 in vitro , and is phosphorylated in a WNK1-dependent manner in cells. Depletion of WNK1 from HeLa cells by using small interfering RNA reduces OSR1 kinase activity. In addition, depletion of either WNK1 or OSR1 reduces NKCC activity, indicating that WNK1 and OSR1 are both required for NKCC function. OSR1 and SPAK are likely links between WNK1 and NKCC in a pathway that contributes to volume regulation and blood pressure homeostasis in mammals.Keywords
This publication has 42 references indexed in Scilit:
- The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinasesBiochemical Journal, 2005
- WNK1: analysis of protein kinase structure, downstream targets, and potential roles in hypertensionCell Research, 2005
- Characterization of OSR1, a Member of the Mammalian Ste20p/Germinal Center Kinase SubfamilyJournal of Biological Chemistry, 2004
- Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRADThe EMBO Journal, 2003
- Cation Chloride Cotransporters Interact with the Stress-related Kinases Ste20-related Proline-Alanine-rich Kinase (SPAK) and Oxidative Stress Response 1 (OSR1)Journal of Biological Chemistry, 2002
- A Regulatory Locus of Phosphorylation in the N Terminus of the Na-K-Cl Cotransporter, NKCC1Journal of Biological Chemistry, 2002
- Human and Murine Phenotypes Associated with Defects in Cation-Chloride CotransportAnnual Review of Physiology, 2002
- Human Hypertension Caused by Mutations in WNK KinasesScience, 2001
- Isolation and characterization of a novel serine threonine kinase gene on chromosome 3p22-21.3Journal of Human Genetics, 1999
- Regulatory interaction of ATP Na+ and Cl- in the turnover cycle of the NaK2Cl cotransporter.The Journal of general physiology, 1993