Gene Symbol: Oxsr1
Description: oxidative-stress responsive 1
Alias: 2210022N24Rik, 2810422B09Rik, AI462649, AW209236, Osr1, mKIAA1101, serine/threonine-protein kinase OSR1, oxidative stress-responsive 1 protein, oxsr1
Species: mouse
Products:     Oxsr1

Top Publications

  1. Vallon V. Regulation of the Na+-Cl- cotransporter by dietary NaCl: a role for WNKs, SPAK, OSR1, and aldosterone. Kidney Int. 2008;74:1373-5 pubmed publisher
    ..which defines an important influence of aldosterone in the phosphorylation and thus activation of the Na(+)-Cl(-) cotransporter (NCC) in response to changes in NaCl intake and implicates the involvement of SPAK/OSR1 kinases and WNKs.
  2. Gagnon K, England R, Delpire E. Characterization of SPAK and OSR1, regulatory kinases of the Na-K-2Cl cotransporter. Mol Cell Biol. 2006;26:689-98 pubmed
    ..b>OSR1, a kinase closely related to SPAK, exhibited similar kinase properties and similar functional activation of NKCC1 ..
  3. Rafiqi F, Zuber A, Glover M, Richardson C, Fleming S, Jovanovic S, et al. Role of the WNK-activated SPAK kinase in regulating blood pressure. EMBO Mol Med. 2010;2:63-75 pubmed publisher
    ..See accompanying Closeup by Maria Castañeda-Bueno and Gerald Gamba (DOI 10.1002/emmm.200900059). ..
  4. Grimm P, Taneja T, Liu J, Coleman R, Chen Y, Delpire E, et al. SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron-specific manner. J Biol Chem. 2012;287:37673-90 pubmed publisher
    STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) and oxidative stress-related kinase (OSR1) activate the potassium-dependent sodium-chloride co-transporter, NKCC2, and thiazide-sensitive sodium-chloride cotransporter, NCC, ..
  5. Chiga M, Rafiqi F, Alessi D, Sohara E, Ohta A, Rai T, et al. Phenotypes of pseudohypoaldosteronism type II caused by the WNK4 D561A missense mutation are dependent on the WNK-OSR1/SPAK kinase cascade. J Cell Sci. 2011;124:1391-5 pubmed publisher
    ..Although previous in vitro studies had suggested the existence of a phosphorylation cascade involving the WNK, OSR1 and SPAK kinases, whether the WNK-OSR1/SPAK cascade is in fact fully responsible for NCC phosphorylation in vivo ..
  6. Lin S, Yu I, Jiang S, Lin S, Chu P, Chen A, et al. Impaired phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter by oxidative stress-responsive kinase-1 deficiency manifests hypotension and Bartter-like syndrome. Proc Natl Acad Sci U S A. 2011;108:17538-43 pubmed publisher
    ..Oxidative stress-responsive kinase-1 (OSR1) is a known upstream regulator of N(K)CCs...
  7. Piechotta K, Lu J, Delpire E. Cation chloride cotransporters interact with the stress-related kinases Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1). J Biol Chem. 2002;277:50812-9 pubmed
    ..serine-threonine kinases Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1) with the cotransporters KCC3, NKCC1, and NKCC2 but not KCC1 and KCC4...
  8. Geng Y, Hoke A, Delpire E. The Ste20 kinases Ste20-related proline-alanine-rich kinase and oxidative-stress response 1 regulate NKCC1 function in sensory neurons. J Biol Chem. 2009;284:14020-8 pubmed publisher
    ..bind and phosphorylate NKCC1: Ste20-related proline-alanine-rich kinase (SPAK) and oxidative-stress response 1 (OSR1)...
  9. McCormick J, Mutig K, Nelson J, Saritas T, Hoorn E, Yang C, et al. A SPAK isoform switch modulates renal salt transport and blood pressure. Cell Metab. 2011;14:352-64 pubmed publisher
    ..transporters (NKCC2 and NCC) along these segments are phosphorylated and activated by WNK kinases, via SPAK and OSR1. Here, we show that a kidney-specific SPAK isoform, which lacks the kinase domain, inhibits phosphorylation of NCC ..

More Information


  1. Köchl R, Thelen F, Vanes L, Brazão T, Fountain K, Xie J, et al. WNK1 kinase balances T cell adhesion versus migration in vivo. Nat Immunol. 2016;17:1075-83 pubmed publisher
    ..regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via the kinases OXSR1 and STK39 and the ion co-transporter SLC12A2...
  2. de los Heros P, Alessi D, Gourlay R, Campbell D, Deak M, MacArtney T, et al. The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters. Biochem J. 2014;458:559-73 pubmed publisher
    ..that the WNK (WNK lysine-deficient protein kinase)-activated SPAK (SPS1-related proline/alanine-rich kinase)/OSR1 (oxidative stress-responsive kinase 1) known to directly phosphorylate and stimulate the N[K]CCs (Na+-K+ ion co-..
  3. Chu P, Cheng C, Wu Y, Fang Y, Chau T, Uchida S, et al. SPAK deficiency corrects pseudohypoaldosteronism II caused by WNK4 mutation. PLoS ONE. 2013;8:e72969 pubmed publisher
    Stimulation of the OSR1 (Oxidative stress-responsive kinase-1)/SPAK [STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase]-NCC (Na(+)-Cl(-) cotransporter) signaling cascade plays an important role in the WNK [With-No-Lysine (K)] ..
  4. Chen W, Yazicioglu M, Cobb M. Characterization of OSR1, a member of the mammalian Ste20p/germinal center kinase subfamily. J Biol Chem. 2004;279:11129-36 pubmed
    ..To explore the possible link to JNK in mammalian cells, we isolated and characterized OSR1 (oxidative stress-responsive 1), one of two human Fray homologs...
  5. Hengl T, Kaneko H, Dauner K, Vocke K, Frings S, Möhrlen F. Molecular components of signal amplification in olfactory sensory cilia. Proc Natl Acad Sci U S A. 2010;107:6052-7 pubmed publisher
    ..Gene silencing experiments revealed that the activity of this transporter depends on the kinases SPAK and OSR1, which are enriched in the cilia together with their own activating kinases, WNK1 and WNK4...
  6. Pasham V, Pathare G, Fajol A, Rexhepaj R, Michael D, Pakladok T, et al. OSR1-sensitive small intestinal Na+ transport. Am J Physiol Gastrointest Liver Physiol. 2012;303:G1212-9 pubmed publisher
    The oxidative stress responsive kinase 1 (OSR1) contributes to WNK (with no K)-dependent regulation of renal tubular salt transport, renal salt excretion, and blood pressure...
  7. Gamba G. Regulation of NKCC2 activity by SPAK truncated isoforms. Am J Physiol Renal Physiol. 2014;306:F49-50 pubmed publisher
  8. Chiga M, Rai T, Yang S, Ohta A, Takizawa T, Sasaki S, et al. Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone. Kidney Int. 2008;74:1403-9 pubmed publisher
    ..that other kinases, such as the oxidative stress response kinase-1/STE20/SPS1-related proline alanine-rich kinase (OSR1/SPAK), also showed increased phosphorylation in these mice...
  9. Terker A, Zhang C, McCormick J, Lazelle R, Zhang C, Meermeier N, et al. Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride. Cell Metab. 2015;21:39-50 pubmed publisher
    ..In the DCT, hyperpolarization activates NCC via WNK kinases, whereas in the adrenal gland, it inhibits aldosterone secretion. These effects work in concert to maintain potassium homeostasis. ..
  10. Pasham V, Rotte A, Yang W, Zelenak C, Bhandaru M, Foller M, et al. OSR1-sensitive regulation of Na+/H+ exchanger activity in dendritic cells. Am J Physiol Cell Physiol. 2012;303:C416-26 pubmed publisher
    The oxidative stress-responsive kinase 1 (OSR1) is activated by WNK (with no K kinases) and in turn stimulates the thiazide-sensitive Na-Cl cotransporter (NCC) and the furosemide-sensitive Na-K-2Cl cotransporter (NKCC), thus contributing ..
  11. Xie J, Yoon J, Yang S, Lin S, Huang C. WNK1 protein kinase regulates embryonic cardiovascular development through the OSR1 signaling cascade. J Biol Chem. 2013;288:8566-74 pubmed publisher
    ..We found that mice with a global deletion of Osr1, which encodes oxidative stress-responsive kinase-1, a protein kinase activated by WNK1, died in utero beginning at ..
  12. Davies M, Fraser S, Galic S, Choy S, Katerelos M, Gleich K, et al. Novel mechanisms of Na+ retention in obesity: phosphorylation of NKCC2 and regulation of SPAK/OSR1 by AMPK. Am J Physiol Renal Physiol. 2014;307:F96-F106 pubmed publisher
    ..Activation of STE-20/SPS1-related proline-alanine-rich protein kinase (SPAK)/oxidative stress responsive 1 kinase (OSR1) was increased in kidneys from HFD-fed mice, and enhanced phosphorylation of NKCC2 at T96/T101 was evident in the ..