WNK1 and OSR1 Regulate the Na+, K+, 2Cl- Cotransporter in HeLa Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Jul 13

PMID 16832045

Citations 96

Authors

Anthony N Anselmo

Svetlana Earnest

Wei Chen

Yu-Chi Juang

Sung Chan Kim

Yingming Zhao

Melanie H Cobb

Affiliations

Soon will be listed here.

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.

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