WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells

Anthony N. Anselmo, Svetlana Earnest, Wei Chen, Yu Chi Juang, Sung Chan Kim, Yingming Zhao, Melanie H. Cobb

Research output: Contribution to journalArticle

126 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)10883-10888
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number29
DOIs
StatePublished - Jul 18 2006

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HeLa Cells
Phosphotransferases
Proline
Alanine
Protein Kinases
Sodium-Potassium-Chloride Symporters
Small Interfering RNA
Lysine
Mammals
Oxidative Stress
Homeostasis
Blood Pressure

Keywords

  • Blood pressure
  • Kinase
  • Osmotic
  • Stress

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells. / Anselmo, Anthony N.; Earnest, Svetlana; Chen, Wei; Juang, Yu Chi; Kim, Sung Chan; Zhao, Yingming; Cobb, Melanie H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 29, 18.07.2006, p. 10883-10888.

Research output: Contribution to journalArticle

Anselmo, Anthony N. ; Earnest, Svetlana ; Chen, Wei ; Juang, Yu Chi ; Kim, Sung Chan ; Zhao, Yingming ; Cobb, Melanie H. / WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 29. pp. 10883-10888.
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AU - Anselmo, Anthony N.

AU - Earnest, Svetlana

AU - Chen, Wei

AU - Juang, Yu Chi

AU - Kim, Sung Chan

AU - Zhao, Yingming

AU - Cobb, Melanie H.

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N2 - 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.

AB - 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.

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KW - Osmotic

KW - Stress

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