title: WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells.
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.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Anselmo
authors.forename: Svetlana
authors.initials: S
authors.lastname: Earnest
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Juang
authors.forename: Sung Chan
authors.initials: SC
authors.lastname: Kim
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Cobb
mesh_terms: D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D000076204:WNK Lysine-Deficient Protein Kinase 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D028021:Sodium-Potassium-Chloride Symporters; C118135:OXSR1 protein, human; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human