OXSR1

Summary

Gene Symbol: OXSR1
Description: oxidative stress responsive 1
Alias: OSR1, serine/threonine-protein kinase OSR1, oxidative stress-responsive 1 protein
Species: human
Products:     OXSR1

Top Publications

  1. Moriguchi T, Urushiyama S, Hisamoto N, Iemura S, Uchida S, Natsume T, et al. WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1. J Biol Chem. 2005;280:42685-93 pubmed
    ..the STE20-related kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1)...
  2. 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...
  3. Vitari A, Thastrup J, Rafiqi F, Deak M, Morrice N, Karlsson H, et al. Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1. Biochem J. 2006;397:223-31 pubmed
    The SPAK (STE20/SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase-1) kinases interact and phosphorylate NKCC1 (Na+-K+-2Cl- co-transporter-1), leading to its activation...
  4. Richardson C, Rafiqi F, Karlsson H, Moleleki N, Vandewalle A, Campbell D, et al. Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1. J Cell Sci. 2008;121:675-84 pubmed publisher
    ..Here, we demonstrate that the SPAK and OSR1 kinases that are activated by WNK1 phosphorylate human NCC at three conserved residues (Thr46, Thr55 and Thr60)...
  5. Filippi B, de los Heros P, Mehellou Y, Navratilova I, Gourlay R, Deak M, et al. MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases. EMBO J. 2011;30:1730-41 pubmed publisher
    ..These new MO25 targets are SPAK/OSR1 kinases, regulators of ion homeostasis and blood pressure, and MST3/MST4/YSK1, involved in controlling development ..
  6. Sarathy A, Wuebbles R, Fontelonga T, Tarchione A, Mathews Griner L, Heredia D, et al. SU9516 Increases α7β1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy. Mol Ther. 2017;25:1395-1407 pubmed publisher
    ..SU9516 inhibitory actions on the p65-NF-κB pro-inflammatory and Ste20-related proline alanine rich kinase (SPAK)/OSR1 signaling pathways...
  7. Neto A, Mercader N, Gomez Skarmeta J. The Osr1 and Osr2 genes act in the pronephric anlage downstream of retinoic acid signaling and upstream of Wnt2b to maintain pectoral fin development. Development. 2012;139:301-11 pubmed publisher
  8. Zhu C, Luong R, Zhuo M, Johnson D, McKenney J, Cunha G, et al. Conditional expression of the androgen receptor induces oncogenic transformation of the mouse prostate. J Biol Chem. 2011;286:33478-88 pubmed publisher
    ..By crossing this AR floxed strain with Osr1-Cre (odd skipped related) mice, in which the Osr1 promoter activates at embryonic day 11...
  9. Trattnig C, Üçal M, Tam Amersdorfer C, Bucko A, Zefferer U, Grünbacher G, et al. MicroRNA-451a overexpression induces accelerated neuronal differentiation of Ntera2/D1 cells and ablation affects neurogenesis in microRNA-451a-/- mice. PLoS ONE. 2018;13:e0207575 pubmed publisher
    ..MiR-451a targets genes MIF, AKT1, CAB39, YWHAZ, RAB14, TSC1, OSR1, POU3F2, TNS4, PSMB8, CXCL16, CDKN2D and IL6R were, moreover, either constantly downregulated or exhibited shifted ..

More Information

Publications118 found, 100 shown here

  1. Zheng S, Krump N, McKenna M, Li Y, Hannemann A, Garrett L, et al. Regulation of erythrocyte Na+/K+/2Cl- cotransport by an oxygen-switched kinase cascade. J Biol Chem. 2019;294:2519-2528 pubmed publisher
    ..This displacement enabled WNK1 to phosphorylate oxidative stress-responsive kinase 1 (OSR1), which, in turn, phosphorylated and activated NKCC1...
  2. AlAmri M, Jeeves M, Mehellou Y. Sequence specific assignment and determination of OSR1 C-terminal domain structure by NMR. Biochem Biophys Res Commun. 2019;512:338-343 pubmed publisher
    The binding of SPAK and OSR1 kinases to their upstream WNK kinases is mediated by the interaction of their highly conserved SPAK and OSR1 C-terminal domain (CTD) to RFx [V/I] peptide sequences from WNK kinases...
  3. Zhang Z, Wang Y, Shi Z, Zhang M. Structure of zebrafish MO25. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013;69:989-93 pubmed publisher
    ..MO25 also promotes the activities of the STE20-family kinases MST3, MST4, STK25, SPAK and OSR1. Zebrafish MO25 was purified and crystallized, and a crystal of zebrafish MO25 diffracted to 2...
  4. Gallolu Kankanamalage S, Karra A, Cobb M. WNK pathways in cancer signaling networks. Cell Commun Signal. 2018;16:72 pubmed publisher
    ..oxidative stress responsive (OSR)1 and SPS/Ste20-related proline-alanine-rich kinase (SPAK), and a multitude of OSR1/SPAK substrates including cation chloride cotransporters...
  5. Stumm J, Vallecillo García P, Vom Hofe Schneider S, Ollitrault D, Schrewe H, Economides A, et al. Odd skipped-related 1 (Osr1) identifies muscle-interstitial fibro-adipogenic progenitors (FAPs) activated by acute injury. Stem Cell Res. 2018;32:8-16 pubmed publisher
    ..We have shown previously that FAPs are derived from cells that express the transcription factor Osr1 during development...
  6. Lu T, Chan C, Ling P, Chao Y, Bao B, Chiang C, et al. MST3 (mammalian Ste20-like protein kinase 3), a novel gene involved in ion homeostasis and renal regulation of blood pressure in spontaneous hypertensive rats. Int Urol Nephrol. 2018;50:2299-2307 pubmed publisher
    ..family kinases, such as proline-alanine-rich Ste20-related kinase (SPAK) and oxidative stress-response protein 1 (OSR1), are regulators of cell volume, ion transport, and hypertension...
  7. Chen W, Wu K, Zhang H, Fu X, Yao F, Yang A. Odd-skipped related transcription factor 1 (OSR1) suppresses tongue squamous cell carcinoma migration and invasion through inhibiting NF-κB pathway. Eur J Pharmacol. 2018;839:33-39 pubmed publisher
    ..Previous studies suggest OSR1 suppresses the progression of gastric cancer and renal cell carcinoma, but its role in TSCC hasn't been studied...
  8. Cornelius R, Si J, Cuevas C, Nelson J, Gratreak B, Pardi R, et al. Renal COP9 Signalosome Deficiency Alters CUL3-KLHL3-WNK Signaling Pathway. J Am Soc Nephrol. 2018;29:2627-2640 pubmed publisher
    ..Activation of WNK4, SPAK, and OSR1 was indicated by higher phosphorylated protein levels and translocation of the proteins into puncta, as observed by ..
  9. Taylor C, An S, Kankanamalage S, Stippec S, Earnest S, Trivedi A, et al. OSR1 regulates a subset of inward rectifier potassium channels via a binding motif variant. Proc Natl Acad Sci U S A. 2018;115:3840-3845 pubmed publisher
    ..signaling pathway to STE20/SPS1-related proline- and alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1) kinase is an important mediator of cell volume and ion transport...
  10. Dbouk H, Weil L, Perera G, Dellinger M, Pearson G, Brekken R, et al. Actions of the protein kinase WNK1 on endothelial cells are differentially mediated by its substrate kinases OSR1 and SPAK. Proc Natl Acad Sci U S A. 2014;111:15999-6004 pubmed publisher
    ..be rescued by endothelial-specific expression of a constitutively active form of the WNK1 substrate protein kinase OSR1 (oxidative stress responsive 1)...
  11. Taylor C, Juang Y, Earnest S, Sengupta S, Goldsmith E, Cobb M. Domain-Swapping Switch Point in Ste20 Protein Kinase SPAK. Biochemistry. 2015;54:5063-71 pubmed publisher
    The related protein kinases SPAK and OSR1 regulate ion homeostasis in part by phosphorylating cation cotransporter family members...
  12. Alessi D, Zhang J, Khanna A, Hochdörfer T, Shang Y, Kahle K. The WNK-SPAK/OSR1 pathway: master regulator of cation-chloride cotransporters. Sci Signal. 2014;7:re3 pubmed publisher
    The WNK-SPAK/OSR1 kinase complex is composed of the kinases WNK (with no lysine) and SPAK (SPS1-related proline/alanine-rich kinase) or the SPAK homolog OSR1 (oxidative stress-responsive kinase 1)...
  13. Li C, Feng M, Shi Z, Hao Q, Song X, Wang W, et al. Structural and biochemical insights into the activation mechanisms of germinal center kinase OSR1. J Biol Chem. 2014;289:35969-78 pubmed publisher
    The oxidative stress-responsive 1 (OSR1) kinase belongs to the mammalian STE20-like kinase family...
  14. Abousaab A, Warsi J, Elvira B, Alesutan I, Hoseinzadeh Z, Lang F. Down-Regulation of Excitatory Amino Acid Transporters EAAT1 and EAAT2 by the Kinases SPAK and OSR1. J Membr Biol. 2015;248:1107-19 pubmed publisher
    SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) are cell volume-sensitive kinases regulated by WNK (with-no-K[Lys]) kinases. SPAK/OSR1 regulate several channels and carriers...
  15. Zhou X, Naguro I, Ichijo H, Watanabe K. Mitogen-activated protein kinases as key players in osmotic stress signaling. Biochim Biophys Acta. 2016;1860:2037-52 pubmed publisher
    ..Based on its activity change during osmotic stress and its regulation of the WNK1-SPAK/OSR1 pathway, ASK3 is expected to play important roles in osmosensing mechanisms and cellular functions related to ..
  16. Orgeur M, Martens M, Leonte G, Nassari S, Bonnin M, Börno S, et al. Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors. Development. 2018;145: pubmed publisher
    ..the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue ..
  17. Roy A, Goodman J, Begum G, Donnelly B, Pittman G, Weinman E, et al. Generation of WNK1 knockout cell lines by CRISPR/Cas-mediated genome editing. Am J Physiol Renal Physiol. 2015;308:F366-76 pubmed publisher
    ..kinases, Ste20- and SPS1-related proline alanine-rich kinase (SPAK) and oxidative stress-responsive kinase 1 (OSR1)...
  18. Cohen P, Alessi D. Kinase drug discovery--what's next in the field?. ACS Chem Biol. 2013;8:96-104 pubmed publisher
    ..in protein kinases underlie many other diseases and conditions, and we also discuss why the protein kinases SPAK/OSR1 and LRRK2 have recently become interesting targets for the treatment of hypertension and Parkinson's disease, ..
  19. Zhang C, Meermeier N, Terker A, Blankenstein K, Singer J, Hadchouel J, et al. Degradation by Cullin 3 and effect on WNK kinases suggest a role of KLHL2 in the pathogenesis of Familial Hyperkalemic Hypertension. Biochem Biophys Res Commun. 2016;469:44-48 pubmed publisher
    ..cotransporter (NCC), which is phosphorylated and activated by the WNK-stimulated Ste20-type kinases, SPAK and OSR1. WNK kinases themselves can be targeted for ubiquitination and degradataion by the CUL3-KLHL3 E3 ubiquitin ligase ..
  20. Liu H, Chen S, Yao X, Li Y, Chen C, Liu J, et al. Histone deacetylases 1 and 2 regulate the transcriptional programs of nephron progenitors and renal vesicles. Development. 2018;145: pubmed publisher
    ..HDAC1/2 interact with the NPC renewal regulators Six2, Osr1 and Sall1, and are co-bound along with Six2 on the Six2 enhancer...
  21. O Shaughnessy K. Gordon Syndrome: a continuing story. Pediatr Nephrol. 2015;30:1903-8 pubmed publisher
    ..years to appreciate that these kinases operated in a cascade with downstream serine/threonine kinases (SPAK and OSR1) actually phosphorylating and activating NCC and the closely related cotransporters NKCC1 and NKCC2...
  22. Park S, Ku S, Ji H, Choi J, Shin D. Ca(2+) is a Regulator of the WNK/OSR1/NKCC Pathway in a Human Salivary Gland Cell Line. Korean J Physiol Pharmacol. 2015;19:249-55 pubmed publisher
    ..cotransporter 1 (NKCC1) through the phosphorylation of oxidative stress responsive kinase 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK)...
  23. Xu J, Liu H, Chai O, Lan Y, Jiang R. Osr1 Interacts Synergistically with Wt1 to Regulate Kidney Organogenesis. PLoS ONE. 2016;11:e0159597 pubmed publisher
    ..Recent studies have associated a variant of the OSR1 gene with reduction of newborn kidney size and function in heterozygotes and neonatal lethality with kidney defects ..
  24. Du E, Lu C, Sheng F, Li C, Li H, Ding N, et al. Analysis of potential genes associated with primary cilia in bladder cancer. Cancer Manag Res. 2018;10:3047-3056 pubmed publisher
    ..tissue samples were analyzed, and five DEGs including CENPF, STIL, AURKA, STK39 and OSR1 were identified...
  25. Lozić B, Krželj V, Kuzmić Prusac I, Kuzmanić Šamija R, Čapkun V, Lasan R, et al. The OSR1 rs12329305 polymorphism contributes to the development of congenital malformations in cases of stillborn/neonatal death. Med Sci Monit. 2014;20:1531-8 pubmed publisher
    ..The polymorphisms of OSR1 rs12329305, rs9936833 near FOXF1, and HOXA1 rs10951154 were genotyped using the TaqMan allelic discrimination assay...
  26. Kim M, Yang H, Kim Y, Kang I, Kim S, Cho Y. Role of nitric oxide and WNK-SPAK/OSR1-KCC2 signaling in daily changes in GABAergic inhibition in the rat dorsal raphe neurons. Neuropharmacology. 2018;135:355-367 pubmed publisher
    ..Total Ste20-related proline alanine rich kinase (SPAK) and oxidative stress response kinase 1 (OSR1) were also higher during daytime than during nighttime, while there were no changes in phosphorylated SPAK and OSR1...
  27. Mandai S, Mori T, Nomura N, Furusho T, Arai Y, Kikuchi H, et al. WNK1 regulates skeletal muscle cell hypertrophy by modulating the nuclear localization and transcriptional activity of FOXO4. Sci Rep. 2018;8:9101 pubmed publisher
    ..signaling pathway linking SPS/STE20-related proline-alanine-rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1) to downstream effector ion transporters...
  28. Tokonami N, Takata T, Beyeler J, Ehrbar I, Yoshifuji A, Christensen E, et al. Uromodulin is expressed in the distal convoluted tubule, where it is critical for regulation of the sodium chloride cotransporter NCC. Kidney Int. 2018;94:701-715 pubmed publisher
    ..studies in HEK cells suggested a facilitating role for uromodulin in NCC phosphorylation, possibly via SPAK-OSR1 modulation...
  29. Karvande A, Kushwaha P, Ahmad N, Adhikary S, Kothari P, Tripathi A, et al. Glucose dependent miR-451a expression contributes to parathyroid hormone mediated osteoblast differentiation. Bone. 2018;117:98-115 pubmed publisher
    ..These actions were mediated through the suppression of Odd-skipped related 1 (Osr1) and activation of Runx2 transcription...
  30. Zhou L, Liu J, Olson P, Zhang K, Wynne J, Xie L. Tbx5 and Osr1 interact to regulate posterior second heart field cell cycle progression for cardiac septation. J Mol Cell Cardiol. 2015;85:1-12 pubmed publisher
    ..Previous studies have demonstrated that Tbx5 regulates Osr1 expression in the second heart field (SHF) of E9.5 mouse embryos...
  31. Cha S, Lim J, Park A, Do J, Lee S, Shin C, et al. Identification of five novel genetic loci related to facial morphology by genome-wide association studies. BMC Genomics. 2018;19:481 pubmed publisher
    ..The OSR1-WDR35 [rs7567283, G allele, beta (se) = -0.536 (0.096), P = 2...
  32. Warsi J, Hosseinzadeh Z, Elvira B, Bissinger R, Shumilina E, Lang F. Regulation of ClC-2 activity by SPAK and OSR1. Kidney Blood Press Res. 2014;39:378-87 pubmed publisher
    SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) are powerful regulators of diverse transport processes...
  33. West C, McDonough A, Masilamani S, Verlander J, Baylis C. Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention. Am J Physiol Renal Physiol. 2015;309:F63-70 pubmed publisher
    ..Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats...
  34. Hoshina A, Kawamoto T, Sueta S, Mae S, Araoka T, Tanaka H, et al. Development of new method to enrich human iPSC-derived renal progenitors using cell surface markers. Sci Rep. 2018;8:6375 pubmed publisher
    ..of four markers, CD9-CD140a+CD140b+CD271+, which could enrich OSR1+SIX2+ renal progenitors...
  35. Terashima A, Mudumana S, Drummond I. Odd skipped related 1 is a negative feedback regulator of nodal-induced endoderm development. Dev Dyn. 2014;243:1571-80 pubmed publisher
    ..Here we identify odd skipped related 1 (osr1), a zinc finger transcription factor, as a new element in Nodal feedback regulation affecting endoderm development...
  36. Davisson M, Cook S, Akeson E, Liu D, Heffner C, Gudis P, et al. Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis. Am J Physiol Renal Physiol. 2015;308:F1335-42 pubmed publisher
    Many genes, including odd-skipped related 1 (Osr1), are involved in regulation of mammalian kidney development...
  37. Begum G, Yuan H, Kahle K, Li L, Wang S, Shi Y, et al. Inhibition of WNK3 Kinase Signaling Reduces Brain Damage and Accelerates Neurological Recovery After Stroke. Stroke. 2015;46:1956-1965 pubmed publisher
    ..downstream Ste20/SPS1-related proline-alanine-rich protein kinase (SPAK) and oxidative stress responsive 1 (OSR1) kinases, comprise an important signaling cascade that regulates the cation-chloride cotransporters...
  38. Warsi J, Elvira B, Bissinger R, Shumilina E, Hosseinzadeh Z, Lang F. Downregulation of peptide transporters PEPT1 and PEPT2 by oxidative stress responsive kinase OSR1. Kidney Blood Press Res. 2014;39:591-9 pubmed publisher
    b>OSR1 (oxidative-stress-responsive kinase 1) participates in the regulation of renal tubular ion transport, cell volume and blood pressure. Whether OSR1 contributes to the regulation of organic solute transport remained; however, elusive...
  39. Mehellou Y, AlAmri M, Dhiani B, Kadri H. C-terminal phosphorylation of SPAK and OSR1 kinases promotes their binding and activation by the scaffolding protein MO25. Biochem Biophys Res Commun. 2018;503:1868-1873 pubmed publisher
    SPAK and OSR1 are two protein kinases that play important roles in regulating the function of numerous ion co-transporters...
  40. Gao Y, Stuart D, Takahishi T, Kohan D. Nephron-Specific Disruption of Nitric Oxide Synthase 3 Causes Hypertension and Impaired Salt Excretion. J Am Heart Assoc. 2018;7: pubmed publisher
    ..Chronic high salt-treated KO mice had modestly decreased total NCC and total SPAK/OSR1 versus controls, however percent phosphorylation of NCC (at T53) and of SPAK/OSR1 was increased...
  41. Fezai M, Elvira B, Borras J, Ben Attia M, Hoseinzadeh Z, Lang F. Negative regulation of the creatine transporter SLC6A8 by SPAK and OSR1. Kidney Blood Press Res. 2014;39:546-54 pubmed publisher
    Transport regulation involves several kinases including SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases...
  42. Futel M, Leclerc C, Le Bouffant R, Buisson I, Néant I, Umbhauer M, et al. TRPP2-dependent Ca2+ signaling in dorso-lateral mesoderm is required for kidney field establishment in Xenopus. J Cell Sci. 2015;128:888-99 pubmed publisher
    ..of pkd2 in the kidney field results in the downregulation of pax8, but not of other kidney field genes (lhx1, osr1 and osr2)...
  43. Elvira B, Munoz C, Borras J, Chen H, Warsi J, Ajay S, et al. SPAK and OSR1 dependent down-regulation of murine renal outer medullary K channel ROMK1. Kidney Blood Press Res. 2014;39:353-60 pubmed publisher
    The kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) participate in the regulation of the NaCl cotransporter NCC and the Na+, K+, 2Cl- cotransporter NKCC2...
  44. Cheng C, Yoon J, Baum M, Huang C. STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb. Am J Physiol Renal Physiol. 2015;308:F437-43 pubmed publisher
    ..5 and 12.5% of WT tubules, respectively. The mRNA levels of related OSR1 kinase and SPAK protease Dnpep in SPAK-KO tubules were not significantly different from WT tubules...
  45. Bazúa Valenti S, Gamba G. Revisiting the NaCl cotransporter regulation by with-no-lysine kinases. Am J Physiol Cell Physiol. 2015;308:C779-91 pubmed publisher
    ..complex and that WNKs modulate the activity of NCC by means of intermediary Ste20-type kinases known as SPAK or OSR1. The understanding of the effect of WNKs on NCC is a complex issue, but recent evidence discussed in this review ..
  46. Ferdaus M, McCormick J. The CUL3/KLHL3-WNK-SPAK/OSR1 pathway as a target for antihypertensive therapy. Am J Physiol Renal Physiol. 2016;310:F1389-96 pubmed publisher
    ..Here, we will describe the mechanisms by which this pathway regulate blood pressure and discuss the potential of targeting it to develop new antihypertensive drugs. ..
  47. Vorontsova I, Lam L, Delpire E, Lim J, Donaldson P. Identification of the WNK-SPAK/OSR1 signaling pathway in rodent and human lenses. Invest Ophthalmol Vis Sci. 2014;56:310-21 pubmed publisher
    ..The expression of with-no-lysine kinase (WNK 1, 3, 4), oxidative stress response kinase 1 (OSR1), and Ste20-like proline alanine rich kinase (SPAK) were determined at either the transcript or protein levels in ..
  48. Fezai M, Elvira B, Warsi J, Ben Attia M, Hosseinzadeh Z, Lang F. Up-Regulation of Intestinal Phosphate Transporter NaPi-IIb (SLC34A2) by the Kinases SPAK and OSR1. Kidney Blood Press Res. 2015;40:555-64 pubmed publisher
    SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), kinases controlled by WNK (with-no-K[Lys] kinase), are powerful regulators of cellular ion transport and blood pressure...
  49. AlAmri M, Kadri H, Alderwick L, Simpkins N, Mehellou Y. Rafoxanide and Closantel Inhibit SPAK and OSR1 Kinases by Binding to a Highly Conserved Allosteric Site on Their C-terminal Domains. ChemMedChem. 2017;12:639-645 pubmed publisher
    SPAK and OSR1 are two protein kinases that have emerged as attractive targets in the discovery of novel antihypertensive agents due to their role in regulating electrolyte balance in vivo...
  50. Toyohara T, Mae S, Sueta S, Inoue T, Yamagishi Y, Kawamoto T, et al. Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice. Stem Cells Transl Med. 2015;4:980-92 pubmed publisher
    ..We established a multistep differentiation protocol for inducing hiPSCs into OSR1+SIX2+ renal progenitors capable of reconstituting three-dimensional proximal renal tubule-like structures in vitro ..
  51. Roy A, Al Qusairi L, Donnelly B, Ronzaud C, Marciszyn A, Gong F, et al. Alternatively spliced proline-rich cassettes link WNK1 to aldosterone action. J Clin Invest. 2015;125:3433-48 pubmed publisher
    ..NCC-activating pathway consists of With-No-Lysine (WNK) kinases and their downstream effector kinases SPAK and OSR1, which phosphorylate NCC directly...
  52. Fuller S, Osborne S, Leonard S, Hardyman M, Vaniotis G, Allen B, et al. Cardiac protein kinases: the cardiomyocyte kinome and differential kinase expression in human failing hearts. Cardiovasc Res. 2015;108:87-98 pubmed publisher
    ..g. CAMKs, cAMP-dependent protein kinase). Other kinases are poorly investigated (e.g. Slk, Stk24, Oxsr1)...
  53. Argaiz E, Gamba G. The regulation of Na+Cl- cotransporter by with-no-lysine kinase 4. Curr Opin Nephrol Hypertens. 2016;25:417-23 pubmed publisher
    ..is low, WNK4 can activate Ste20-related, proline-alanine-rich kinase (SPAK)/oxidative stress responsive kinase 1 (OSR1) and thus the NCC...
  54. Penton D, Czogalla J, Wengi A, Himmerkus N, Loffing Cueni D, Carrel M, et al. Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl- -dependent and independent mechanisms. J Physiol. 2016;594:6319-6331 pubmed publisher
    ..The Cl- -dependent pathway involves the SPAK/OSR1 kinases, whereas the Cl- independent pathway may include additional signalling cascades...
  55. Shekarabi M, Zhang J, Khanna A, Ellison D, Delpire E, Kahle K. WNK Kinase Signaling in Ion Homeostasis and Human Disease. Cell Metab. 2017;25:285-299 pubmed publisher
    WNK kinases, along with their upstream regulators (CUL3/KLHL3) and downstream targets (the SPAK/OSR1 kinases and the cation-Cl- cotransporters [CCCs]), comprise a signaling cascade essential for ion homeostasis in the kidney ..
  56. Sepponen K, Lundin K, Knuus K, Väyrynen P, Raivio T, Tapanainen J, et al. The Role of Sequential BMP Signaling in Directing Human Embryonic Stem Cells to Bipotential Gonadal Cells. J Clin Endocrinol Metab. 2017;102:4303-4314 pubmed publisher
    ..The two most efficient protocols consistently upregulated IM markers LHX1, PAX2, and OSR1 at days 2 to 4 and bipotential gonadal markers EMX2, GATA4, WT1, and LHX9 at day 8 of culture...
  57. Hadchouel J, Ellison D, Gamba G. Regulation of Renal Electrolyte Transport by WNK and SPAK-OSR1 Kinases. Annu Rev Physiol. 2016;78:367-89 pubmed publisher
    ..the modulation of NCC occurs via the phosphorylation by WNKs of other serine-threonine kinases known as SPAK-OSR1. In contrast, the process of regulating the channels is independent of SPAK-OSR1...
  58. 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...
  59. Sun Q, Wu Y, Jonusaite S, Pleinis J, Humphreys J, He H, et al. Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian Tubule. J Am Soc Nephrol. 2018;29:1449-1461 pubmed publisher
    ..homolog of mammalian Ste20-related proline/alanine-rich kinase (SPAK), and oxidative stress-responsive 1 protein (OSR1)...
  60. Shukuya K, Ogura S, Tokuhara Y, Okubo S, Yatomi Y, Tozuka M, et al. Novel round cells in urine sediment and their clinical implications. Clin Chim Acta. 2016;457:142-9 pubmed publisher
    ..Also it was positive for undifferentiated cell markers, including PAX2, WT1, OSR1, and SIX2...
  61. Koumangoye R, Delpire E. The Ste20 kinases SPAK and OSR1 travel between cells through exosomes. Am J Physiol Cell Physiol. 2016;311:C43-53 pubmed publisher
    Proteomics studies have identified Ste20-related proline/alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1) in exosomes isolated from body fluids such as blood, saliva, and urine...
  62. Zhang Y, Yuan Y, Liang P, Guo X, Ying Y, Shu X, et al. OSR1 is a novel epigenetic silenced tumor suppressor regulating invasion and proliferation in renal cell carcinoma. Oncotarget. 2017;8:30008-30018 pubmed publisher
    ..Here, we found that odd-skipped related transcription factor 1 (OSR1) was downregulated in 769-P and 786-O cells due to promoter CpG methylation...
  63. Borrás J, Salker M, Elvira B, Warsi J, Fezai M, Hoseinzadeh Z, et al. SPAK and OSR1 Sensitivity of Excitatory Amino Acid Transporter EAAT3. Nephron. 2015;130:221-8 pubmed publisher
    ..involved in the regulation of epithelial transport include SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1). SPAK and OSR1 are both regulated by WNK (with-no-K(Lys)) kinases...
  64. Elvira B, Warsi J, Fezai M, Munoz C, Lang F. SPAK and OSR1 Sensitive Cell Membrane Protein Abundance and Activity of KCNQ1/E1 K+ Channels. Cell Physiol Biochem. 2015;37:2032-42 pubmed publisher
    ..in regulation of epithelial transport and cell volume include SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases...
  65. Castañeda Bueno M, Arroyo J, Zhang J, Puthumana J, Yarborough O, Shibata S, et al. Phosphorylation by PKC and PKA regulate the kinase activity and downstream signaling of WNK4. Proc Natl Acad Sci U S A. 2017;114:E879-E886 pubmed publisher
    ..WNK4 phosphorylates the kinases SPAK (Ste20-related proline alanine-rich kinase) and OSR1 (oxidative stress responsive kinase), which then phosphorylate and activate the renal Na-Cl cotransporter (NCC)...
  66. 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, ..
  67. Ponce Coria J, Markadieu N, Austin T, Flammang L, Rios K, Welling P, et al. A novel Ste20-related proline/alanine-rich kinase (SPAK)-independent pathway involving calcium-binding protein 39 (Cab39) and serine threonine kinase with no lysine member 4 (WNK4) in the activation of Na-K-Cl cotransporters. J Biol Chem. 2014;289:17680-8 pubmed publisher
    ..Serine threonine kinase WNK4 (With No K = lysine member 4) and members of the Ste20 kinase family, namely SPAK and OSR1 (Ste20-related proline/alanine-rich kinase, Oxidative stress-responsive kinase) govern phosphorylation...
  68. Huang Z, He L, Huang D, Lei S, Gao J. Icariin protects rats against 5/6 nephrectomy-induced chronic kidney failure by increasing the number of renal stem cells. BMC Complement Altern Med. 2015;15:378 pubmed publisher
    ..Moreover, ccariin significantly increased the expression of CD24, CD133, Osr1, and Nanog in remnant kidney and the numbers of CD133(+)/CD24(+) renal stem/progenitor cells...
  69. Maruyama J, Kobayashi Y, Umeda T, Vandewalle A, Takeda K, Ichijo H, et al. Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway. Sci Rep. 2016;6:18710 pubmed publisher
    The With No lysine [K] (WNK)-Ste20-related proline/alanine-rich kinase (SPAK)/oxidative stress-responsive kinase 1 (OSR1) pathway has been reported to be a crucial signaling pathway for triggering pseudohypoaldosteronism type II (PHAII), ..
  70. Brandt A, Löhers K, Beier M, Leube B, de Torres C, Mora J, et al. Establishment of a Conditionally Immortalized Wilms Tumor Cell Line with a Homozygous WT1 Deletion within a Heterozygous 11p13 Deletion and UPD Limited to 11p15. PLoS ONE. 2016;11:e0155561 pubmed publisher
    ..Here we studied the expression of several genes expressed in early kidney development, e.g. FOXD1, PAX3, SIX1, OSR1, OSR2 and MEIS1 and show that these are expressed at similar levels in the parental and the immortalized Wilms10 ..
  71. Rowan C, Sheybani Deloui S, Rosenblum N. Origin and Function of the Renal Stroma in Health and Disease. Results Probl Cell Differ. 2017;60:205-229 pubmed publisher
    ..Next, we review the specification of stromal cells from the Osr1+ intermediate mesoderm and T+ presomitic mesoderm during embryogenesis and stromal cell differentiation...
  72. Rutledge H, Baran Gale J, de Villena F, Chesler E, Churchill G, Sethupathy P, et al. Identification of microRNAs associated with allergic airway disease using a genetically diverse mouse population. BMC Genomics. 2015;16:633 pubmed publisher
    ..a miR-31 inhibitor revealed two target genes in common with miR-31 targets correlated with neutrophils, namely Oxsr1 and Nsf...
  73. Tahmasbpour E, Ghanei M, Qazvini A, Vahedi E, Panahi Y. Gene expression profile of oxidative stress and antioxidant defense in lung tissue of patients exposed to sulfur mustard. Mutat Res Genet Toxicol Environ Mutagen. 2016;800-801:12-21 pubmed publisher
    ..33%) genes were significantly downregulated (p<0.05). Among the most upregulated genes were OS responsive-1 (OXSR1), forkhead box M1 (FOXM1), and glutathione peroxidase-2 (GPX2), while metallothionein-3 (MT3) and glutathione ..
  74. Ishizawa K, Xu N, Loffing J, Lifton R, Fujita T, Uchida S, et al. Potassium depletion stimulates Na-Cl cotransporter via phosphorylation and inactivation of the ubiquitin ligase Kelch-like 3. Biochem Biophys Res Commun. 2016;480:745-751 pubmed publisher
    ..WNK4, and activation of the downstream kinases SPAK (STE20/SPS1-related proline-alanine-rich protein kinase) and OSR1 (oxidative stress-responsive 1), resulting in NCC phosphorylation and its accumulation at the plasma membrane...
  75. Kozlov S, Waardenberg A, Engholm Keller K, Arthur J, Graham M, Lavin M. Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen. Mol Cell Proteomics. 2016;15:1032-47 pubmed publisher
    ..We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM-dependence ..
  76. Ferdaus M, Barber K, López Cayuqueo K, Terker A, Argaiz E, Gassaway B, et al. SPAK and OSR1 play essential roles in potassium homeostasis through actions on the distal convoluted tubule. J Physiol. 2016;594:4945-66 pubmed publisher
    STE20 (Sterile 20)/SPS-1 related proline/alanine-rich kinase (SPAK) and oxidative stress-response kinase-1 (OSR1) phosphorylate and activate the renal Na(+) -K(+) -2Cl(-) cotransporter 2 (NKCC2) and Na(+) Cl(-) cotransporter (NCC)...
  77. Mercado A, de los Heros P, Melo Z, Chavez Canales M, Murillo de Ozores A, Moreno E, et al. With no lysine L-WNK1 isoforms are negative regulators of the K+-Cl- cotransporters. Am J Physiol Cell Physiol. 2016;311:C54-66 pubmed publisher
    ..Elimination of the STE20 proline-alanine rich kinase (SPAK)/oxidative stress-responsive kinase (OSR1) binding site or the HQ motif required for the WNK-WNK interaction prevented the effect of L-WNK1 on KCCs, ..
  78. Han L, Xu J, Grigg E, Slack M, Chaturvedi P, Jiang R, et al. Osr1 functions downstream of Hedgehog pathway to regulate foregut development. Dev Biol. 2017;427:72-83 pubmed publisher
    ..We show that the zinc finger transcription factor Osr1 is a novel HH target as Osr1 expression in the foregut mesenchyme depends on HH signaling and the effector of HH ..
  79. Hashimoto H, Nomura N, Shoda W, Isobe K, Kikuchi H, Yamamoto K, et al. Metformin increases urinary sodium excretion by reducing phosphorylation of the sodium-chloride cotransporter. Metabolism. 2018;85:23-31 pubmed publisher
    ..WNK-OSR1/SPAK kinase signals were not involved in this inactivation effect of metformin on NCC...
  80. Fezai M, Ahmed M, Hosseinzadeh Z, Elvira B, Lang F. SPAK and OSR1 Sensitive Kir2.1 K+ Channels. Neurosignals. 2015;23:20-33 pubmed publisher
    ..sensitive to the transporter and channels regulating kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are in turn regulated by WNK (with-no-K[Lys]) kinases...
  81. Shoda W, Nomura N, Ando F, Mori Y, Mori T, Sohara E, et al. Calcineurin inhibitors block sodium-chloride cotransporter dephosphorylation in response to high potassium intake. Kidney Int. 2017;91:402-411 pubmed publisher
    ..There was no significant difference in WNK4, OSR1, and SPAK expression after high potassium intake, even after tacrolimus and W7 treatment...
  82. O Brien L, Guo Q, Bahrami Samani E, Park J, Hasso S, Lee Y, et al. Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies. PLoS Genet. 2018;14:e1007181 pubmed publisher
    ..Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors...
  83. Arion D, Lewis D. Altered expression of regulators of the cortical chloride transporters NKCC1 and KCC2 in schizophrenia. Arch Gen Psychiatry. 2011;68:21-31 pubmed publisher
    ..The activities of these transporters are in turn regulated by a network of serine-threonine kinases that includes OXSR1, STK39, and the WNK kinases WNK1, WNK3, and WNK4...
  84. Zhang K, Xiang M, Zhou L, Liu J, Curry N, Heine Suñer D, et al. Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation. Hum Mol Genet. 2016;25:1140-51 pubmed publisher
    ..Our previous studies have demonstrated a genetic interaction between Tbx5 and Osr1 in the second heart field (SHF) for atrial septation...
  85. Kasagi Y, Takahashi D, Aida T, Nishida H, Nomura N, Zeniya M, et al. Impaired degradation of medullary WNK4 in the kidneys of KLHL2 knockout mice. Biochem Biophys Res Commun. 2017;487:368-374 pubmed publisher
    ..WNK4 increases levels of WNKs because of impaired ubiquitination, leading to abnormal over-activation of the WNK-OSR1/SPAK-NCC cascade in the kidney's distal convoluted tubules (DCT)...
  86. Zhou Y, Sun W, Chen N, Xu C, Wang X, Dong K, et al. Discovery of NKCC1 as a potential therapeutic target to inhibit hepatocellular carcinoma cell growth and metastasis. Oncotarget. 2017;8:66328-66342 pubmed publisher
    ..Further results suggested that NKCC1 promotes the invasion ability via MMP-2 activity, and that the WNK1/OSR1/NKCC1 signal pathway might play roles in HCC metastasis...
  87. Villa F, Deak M, Alessi D, van Aalten D. Structure of the OSR1 kinase, a hypertension drug target. Proteins. 2008;73:1082-7 pubmed publisher
  88. Chen L, Zhao W, Tian W, Guo J, Jiang F, Jin L, et al. STK39 is an independent risk factor for male hypertension in Han Chinese. Int J Cardiol. 2012;154:122-7 pubmed publisher
    STK39 interacts with OXSR1 and phosphorylates the sodium-chloride co-transporter (SLC12A3), which plays a critical role in regulating the salt/water balance and blood pressure...
  89. Perens E, Garavito Aguilar Z, Guio Vega G, Peña K, Schindler Y, Yelon D. Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm. elife. 2016;5: pubmed publisher
    ..Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development...
  90. 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...
  91. 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-..
  92. Cusick J, Xu L, Bin L, Han K, Shu H. Identification of RELT homologues that associate with RELT and are phosphorylated by OSR1. Biochem Biophys Res Commun. 2006;340:535-43 pubmed
    ..b>OSR1 was identified through a yeast two-hybrid screen utilizing the intracellular portion of RELL1 as bait, and OSR1 was ..