Gene Symbol: Stk39
Description: serine/threonine kinase 39
Alias: AW227544, AW556857, DCHT, RF005, Rnl5, SPAK, STE20/SPS1-related proline-alanine-rich protein kinase, Ste-20 related kinase, kidney-specific SPAK, serine/threonine kinase 39, STE20/SPS1 homolog, serine/threonine-protein kinase 39, ste-20-related kinase
Species: mouse
Products:     Stk39

Top Publications

  1. Richardson C, Sakamoto K, de los Heros P, Deak M, Campbell D, Prescott A, et al. Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways. J Cell Sci. 2011;124:789-800 pubmed publisher
    ..We demonstrate that hypotonic low-chloride conditions that activate the WNK1-SPAK and OSR1 pathway promote phosphorylation of NKCC2 isoforms (A, B and F) at five residues (Ser91, Thr95, Thr100, ..
  2. Yang S, Lo Y, Wu C, Lin S, Yeh C, Chu P, et al. SPAK-knockout mice manifest Gitelman syndrome and impaired vasoconstriction. J Am Soc Nephrol. 2010;21:1868-77 pubmed publisher
    Polymorphisms in the gene encoding sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) associate with hypertension susceptibility in humans...
  3. Gagnon K, Delpire E. On the substrate recognition and negative regulation of SPAK, a kinase modulating Na+-K+-2Cl- cotransport activity. Am J Physiol Cell Physiol. 2010;299:C614-20 pubmed publisher
    Threonines targeted by Ste20-related proline-alanine-rich kinase (SPAK) for phosphorylation have been identified in Na+-K+-2Cl(-) cotransporter type 1 (NKCC1), NKCC2, and Na+-Cl(-) cotransporter (NCC)...
  4. 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
    ..WNK kinases phosphorylate and activate the STE20/SPS1-related proline/alanine-rich kinase (SPAK) protein kinase, which phosphorylates and stimulates the key Na(+):Cl(-) cotransporter (NCC) and Na(+):K(+):2Cl(-) ..
  5. Yan Y, Dalmasso G, Nguyen H, Obertone T, Charrier Hisamuddin L, Sitaraman S, et al. Nuclear factor-kappaB is a critical mediator of Ste20-like proline-/alanine-rich kinase regulation in intestinal inflammation. Am J Pathol. 2008;173:1013-28 pubmed publisher
    ..Here we show that the expression of colonic Ste20-like proline-/alanine-rich kinase (SPAK) that lacks a PAPA box and an F-alpha helix loop is increased in patients with IBD...
  6. 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
    ..we report the interaction of the stress-related 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...
  7. 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
    ..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 and whether ..
  8. 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.
  9. 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
    ..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...

More Information


  1. Gagnon K, England R, Delpire E. A single binding motif is required for SPAK activation of the Na-K-2Cl cotransporter. Cell Physiol Biochem. 2007;20:131-42 pubmed
    b>SPAK (Ste20p-related proline alanine-rich kinase) phosphorylates and activates NKCC1 (Na-K-2Cl cotransporter) in the presence of another serine/threonine kinase WNK4 (With No lysine (K))...
  2. Piechotta K, Garbarini N, England R, Delpire E. Characterization of the interaction of the stress kinase SPAK with the Na+-K+-2Cl- cotransporter in the nervous system: evidence for a scaffolding role of the kinase. J Biol Chem. 2003;278:52848-56 pubmed
    ..basal and activated conditions in the presence and absence of binding of Ste20-related proline-alanine-rich kinase (SPAK)...
  3. San Cristobal P, Pacheco Alvarez D, Richardson C, Ring A, Vazquez N, Rafiqi F, et al. Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway. Proc Natl Acad Sci U S A. 2009;106:4384-9 pubmed publisher
    ..AngII's effect on NCC is also dependent on the kinase SPAK because dominant-negative SPAK or elimination of the SPAK binding motif in NCC prevent activation of NCC by AngII ..
  4. 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
    ..identified two Ste20-like kinases that bind and phosphorylate NKCC1: Ste20-related proline-alanine-rich kinase (SPAK) and oxidative-stress response 1 (OSR1)...
  5. Johnston A, Naselli G, Gonez L, Martin R, Harrison L, Deaizpurua H. SPAK, a STE20/SPS1-related kinase that activates the p38 pathway. Oncogene. 2000;19:4290-7 pubmed
    We have cloned a member of the STE20/SPS1 protein kinase family from a transformed rat pancreatic beta cell line. SPAK (STE20/SPS1-related, proline alanine-rich kinase) belongs to the SPS1 subfamily of STE20 kinases and is highly ..
  6. 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, ..
  7. 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
    ..NaCl transporters (NKCC2 and NCC) along these segments are phosphorylated and activated by WNK kinases, via SPAK and OSR1...
  8. 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
    Our recent studies demonstrate that SPAK (Ste20p-related Proline Alanine-rich Kinase), in combination with WNK4 [With No lysine (K) kinase], phosphorylates and stimulates the Na-K-2Cl cotransporter (NKCC1), whereas catalytically inactive ..
  9. Gagnon K, England R, Delpire E. Volume sensitivity of cation-Cl- cotransporters is modulated by the interaction of two kinases: Ste20-related proline-alanine-rich kinase and WNK4. Am J Physiol Cell Physiol. 2006;290:C134-42 pubmed
    In the present study, we have demonstrated functional interaction between Ste20-related proline-alanine-rich kinase (SPAK), WNK4 [with no lysine (K)], and the widely expressed Na+-K+-2Cl- cotransporter type 1 (NKCC1)...
  10. Yang S, Huang C, Chen H, Tung C, Shih H, Liu Y. Effects of SPAK knockout on sensorimotor gating, novelty exploration, and brain area-dependent expressions of NKCC1 and KCC2 in a mouse model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2015;61:30-6 pubmed publisher
    b>SPAK (Sterile 20/SPS1-related proline/alanine-rich kinase) is a protein kinase belonging to the mitogen-activated protein kinase (MAPK) superfamily that has been found to be extensively distributed across the body...
  11. Bergaya S, Faure S, Baudrie V, Rio M, Escoubet B, Bonnin P, et al. WNK1 regulates vasoconstriction and blood pressure response to ? 1-adrenergic stimulation in mice. Hypertension. 2011;58:439-45 pubmed publisher
    ..These alterations in vascular tone were associated with a decreased phosphorylation level of the WNK1 substrate SPAK (STE20/SPS1-related proline/alanine-rich kinase) and its target NKCC1 (Na(+)-K(+)-2Cl(-) cotransporter 1) in Wnk1(+/..
  12. 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...
  13. Yan Y, Laroui H, Ingersoll S, Ayyadurai S, Charania M, Yang S, et al. Overexpression of Ste20-related proline/alanine-rich kinase exacerbates experimental colitis in mice. J Immunol. 2011;187:1496-505 pubmed publisher
    ..Colonic Ste20-like proline/alanine-rich kinase (SPAK) plays a role in intestinal inflammation, but its underlying mechanisms need to be defined...
  14. Grimm P, Lazo Fernández Y, Delpire E, Wall S, Dorsey S, Weinman E, et al. Integrated compensatory network is activated in the absence of NCC phosphorylation. J Clin Invest. 2015;125:2136-50 pubmed publisher
    ..Here, we evaluated compensatory pathways in SPAK kinase-deficient mice, which are unable to activate the thiazide-sensitive sodium chloride cotransporter NCC (..
  15. Reiche J, Theilig F, Rafiqi F, Carlo A, Militz D, Mutig K, et al. SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na(+)-K(+)-Cl(-) cotransporter 2. Mol Cell Biol. 2010;30:3027-37 pubmed publisher
    ..SORLA functionally interacts with Ste-20-related proline-alanine-rich kinase (SPAK), an activator of NKCC2, and receptor deficiency is associated with missorting of SPAK...
  16. Markadieu N, Rios K, Spiller B, McDonald W, Welling P, Delpire E. Short forms of Ste20-related proline/alanine-rich kinase (SPAK) in the kidney are created by aspartyl aminopeptidase (Dnpep)-mediated proteolytic cleavage. J Biol Chem. 2014;289:29273-84 pubmed publisher
    The Ste20-related kinase SPAK regulates sodium, potassium, and chloride transport in a variety of tissues. Recently, SPAK fragments, which lack the catalytic domain and are inhibitory to Na(+) transporters, have been detected in kidney...
  17. Zanou N, Mondin L, Fuster C, Seghers F, Dufour I, de Clippele M, et al. Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres. J Physiol. 2015;593:3849-63 pubmed publisher
    ..Hyperosmotic shock also induces phosphorylation of STE20/SPS1-related proline/alanine-rich kinase (SPAK)...
  18. Zhao H, Nepomuceno R, Gao X, Foley L, Wang S, Begum G, et al. Deletion of the WNK3-SPAK kinase complex in mice improves radiographic and clinical outcomes in malignant cerebral edema after ischemic stroke. J Cereb Blood Flow Metab. 2017;37:550-563 pubmed publisher
    The WNK-SPAK kinase signaling pathway controls renal NaCl reabsorption and systemic blood pressure by regulating ion transporters and channels...
  19. Zeniya M, Sohara E, Kita S, Iwamoto T, Susa K, Mori T, et al. Dietary salt intake regulates WNK3-SPAK-NKCC1 phosphorylation cascade in mouse aorta through angiotensin II. Hypertension. 2013;62:872-8 pubmed publisher
    ..Recently, the with-no-lysine kinase (WNK)-STE20/SPS1-related proline/alanine-rich kinase (SPAK)-NKCC1 phosphorylation cascade in vascular smooth muscle cells was found to be important in the regulation of ..
  20. 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)] ..
  21. Yang L, Cai X, Zhou J, Chen S, Chen Y, Chen Z, et al. STE20/SPS1-related proline/alanine-rich kinase is involved in plasticity of GABA signaling function in a mouse model of acquired epilepsy. PLoS ONE. 2013;8:e74614 pubmed publisher
    ..STE20/SPS1-related proline/alanine-rich kinase (SPAK) is known as an indirect regulator of [Cl(-)]i for its activation of Na-K-2 Cl(-)co-transporters (NKCC) and ..
  22. Geng Y, Byun N, Delpire E. Behavioral analysis of Ste20 kinase SPAK knockout mice. Behav Brain Res. 2010;208:377-82 pubmed publisher
    SPAK/STK39 is a mammalian protein kinase involved in the regulation of inorganic ion transport mechanisms known to modulate GABAergic neurotransmission in the both central and the peripheral nervous systems...
  23. 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
    ..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 the rat and human lenses by reverse-transcriptase ..
  24. Denmark A, Tien D, Wong K, Chung A, Cachat J, Goodspeed J, et al. The effects of chronic social defeat stress on mouse self-grooming behavior and its patterning. Behav Brain Res. 2010;208:553-9 pubmed publisher
    ..These findings indicate that chronic social stress modulates grooming behavior in mice, thus illustrating the importance of grooming phenotypes for neurobehavioral stress research. ..
  25. Lin T, Yang S, Hua K, Tsai Y, Lin S, Ka S. SPAK plays a pathogenic role in IgA nephropathy through the activation of NF-?B/MAPKs signaling pathway. Free Radic Biol Med. 2016;99:214-224 pubmed publisher
    Sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) can stimulate production of proinflammatory cytokines and interact with inflammation-related molecules...
  26. 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)...
  27. Gamba G. Regulation of NKCC2 activity by SPAK truncated isoforms. Am J Physiol Renal Physiol. 2014;306:F49-50 pubmed publisher
  28. Yan Y, Dalmasso G, Nguyen H, Obertone T, Sitaraman S, Merlin D. Ste20-related proline/alanine-rich kinase (SPAK) regulated transcriptionally by hyperosmolarity is involved in intestinal barrier function. PLoS ONE. 2009;4:e5049 pubmed publisher
    The Ste20-related protein proline/alanine-rich kinase (SPAK) plays important roles in cellular functions such as cell differentiation and regulation of chloride transport, but its roles in pathogenesis of intestinal inflammation remain ..
  29. 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...
  30. 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
    b>SPAK [STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase] kinase consists of a full-length (FL-) and an alternatively spliced kidney-specific (KS-) isoform...
  31. Castañeda Bueno M, Cervantes Pérez L, Rojas Vega L, Arroyo Garza I, Vazquez N, Moreno E, et al. Modulation of NCC activity by low and high K(+) intake: insights into the signaling pathways involved. Am J Physiol Renal Physiol. 2014;306:F1507-19 pubmed publisher
    ..used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K(+) diets...
  32. 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. ..
  33. 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...
  34. 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
    ..5-fold. 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 ..
  35. Yang D, Li Q, So I, Huang C, Ando H, Mizutani A, et al. IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway. J Clin Invest. 2011;121:956-65 pubmed publisher
    ..In contrast, silencing the with-no-lysine (WNK) kinases and Ste20-related proline/alanine-rich kinase (SPAK) increased secretion...
  36. Zhang J, Siew K, MacArtney T, O Shaughnessy K, Alessi D. Critical role of the SPAK protein kinase CCT domain in controlling blood pressure. Hum Mol Genet. 2015;24:4545-58 pubmed publisher
    The STE20/SPS1-related proline/alanine-rich kinase (SPAK) controls blood pressure (BP) by phosphorylating and stimulating the Na-Cl (NCC) and Na-K-2Cl (NKCC2) co-transporters, which regulate salt reabsorption in the kidney...
  37. Elvira B, Blecua M, Luo D, Yang W, Shumilina E, Munoz C, et al. SPAK-sensitive regulation of glucose transporter SGLT1. J Membr Biol. 2014;247:1191-7 pubmed publisher
    The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK is a powerful regulator of ion transport...
  38. Wade J, Liu J, Coleman R, Grimm P, Delpire E, Welling P. SPAK-mediated NCC regulation in response to low-K+ diet. Am J Physiol Renal Physiol. 2015;308:F923-31 pubmed publisher
    ..Since recent work has shown that the STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) can function to stimulate NCC by phosphorylation of specific N-terminal sites, we investigated whether the NCC ..
  39. Pathare G, Foller M, Michael D, Walker B, Hierlmeier M, Mannheim J, et al. Enhanced FGF23 serum concentrations and phosphaturia in gene targeted mice expressing WNK-resistant SPAK. Kidney Blood Press Res. 2012;36:355-64 pubmed publisher
    The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase (SPAK) regulates the renal thiazide sensitive NaCl cotransporter (NCC) and the renal furosemide sensitive Na+, K+, 2Cl- cotransporter (NKCC2) and thus participates in the ..
  40. Grimm P, Coleman R, Delpire E, Welling P. Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal Tubules. J Am Soc Nephrol. 2017;28:2597-2606 pubmed publisher
    ..To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich ..
  41. Park H, Curry J, McCormick J. Regulation of NKCC2 activity by inhibitory SPAK isoforms: KS-SPAK is a more potent inhibitor than SPAK2. Am J Physiol Renal Physiol. 2013;305:F1687-96 pubmed publisher
    ..cotransporter (NCC) are phosphorylated and activated by the kinases Ste20-related proline alanine-rich kinase (SPAK) and oxidative stress-responsive kinase (OSR1), and their targeted disruption in mice causes phenotypes resembling ..
  42. 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
    ..We demonstrate 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 ..
  43. Fang Y, Yang S, Cheng C, Tseng M, Hsu H, Lin S. Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway. Sci Rep. 2016;6:18360 pubmed publisher
    ..We examined the role of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and with-no-lysine kinase 4 (WNK4) on expression of NCC in mouse models of CMA...
  44. 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...
  45. 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
    ..required for cord formation in HUVECs, but the actions of the two major WNK1 effectors, OSR1 and its close relative SPAK (STE20/SPS1-related proline-, alanine-rich kinase), are distinct...
  46. Ahmed M, Salker M, Elvira B, Umbach A, Fakhri H, Saeed A, et al. SPAK Sensitive Regulation of the Epithelial Na Channel ENaC. Kidney Blood Press Res. 2015;40:335-43 pubmed publisher
    The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na(+),K(+),2Cl(-) cotransport and thus renal salt excretion...
  47. Zhang Y, Viennois E, Xiao B, Baker M, Yang S, Okoro I, et al. Knockout of Ste20-like proline/alanine-rich kinase (SPAK) attenuates intestinal inflammation in mice. Am J Pathol. 2013;182:1617-28 pubmed publisher
    ..Ste20-like proline/alanine-rich kinase (SPAK) plays a role in intestinal inflammation, but the underlying mechanisms need to be defined...
  48. Sid B, Miranda L, Vertommen D, Viollet B, Rider M. Stimulation of human and mouse erythrocyte Na(+)-K(+)-2Cl(-) cotransport by osmotic shrinkage does not involve AMP-activated protein kinase, but is associated with STE20/SPS1-related proline/alanine-rich kinase activation. J Physiol. 2010;588:2315-28 pubmed publisher
    ..human and mouse RBCs led to activation loop phosphorylation of the STE20/SPS1-related proline/alanine-rich kinase (SPAK) at Thr233, which was accompanied by phosphorylation of NKCC1 at Thr203/207/212, one of which (Thr207) is ..
  49. Balatoni C, Dawson D, Suh J, Sherman M, Sanders G, Hong J, et al. Epigenetic silencing of Stk39 in B-cell lymphoma inhibits apoptosis from genotoxic stress. Am J Pathol. 2009;175:1653-61 pubmed publisher
    ..patterns in TCL1-tg B-cell lymphomas identified many lymphoma-specific candidate hypermethylated genes, including Stk39. The Stk39 encoded protein, sterile 20-like-related proline-alanine-rich kinase (SPAK), regulates cell stress ..