Gene Symbol: Stk39
Description: serine threonine kinase 39
Alias: Spak, STE20/SPS1-related proline-alanine-rich protein kinase, PS/TK, PSTK1, Ste-20 related kinase, pancreatic serine/threonine-protein kinase, serine/threonine-protein kinase 39, ste-20-related kinase
Species: rat
Products:     Stk39

Top Publications

  1. 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...
  2. Dowd B, Forbush B. PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of the Na-K-Cl cotransporter (NKCC1). J Biol Chem. 2003;278:27347-53 pubmed
    ..Lu, J., and Delpire, E. (2002) J. Biol. Chem. 277, 50812-50819) reported the binding of PASK (also referred as SPAK (STE20/SPS1-related proline-alanine-rich kinase)) and OSR1 (oxidative stress response kinase) to cation-chloride ..
  3. Vitari A, Deak M, Morrice N, Alessi D. The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases. Biochem J. 2005;391:17-24 pubmed
    ..associated with a protein kinase of the STE20 family termed 'STE20/SPS1-related proline/alanine-rich kinase' (SPAK)...
  4. 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...
  5. Ushiro H, Tsutsumi T, Suzuki K, Kayahara T, Nakano K. Molecular cloning and characterization of a novel Ste20-related protein kinase enriched in neurons and transporting epithelia. Arch Biochem Biophys. 1998;355:233-40 pubmed
    ..Subcellular fractionation showed that PASK was present in both the cytosol and the Triton X-100-insoluble cytoskeletal fraction in brain. ..
  6. 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 ..
  7. 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...
  8. 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...
  9. 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)...

More Information


  1. Miao N, Fung B, Sanchez R, Lydon J, Barker D, Pang K. Isolation and expression of PASK, a serine/threonine kinase, during rat embryonic development, with special emphasis on the pancreas. J Histochem Cytochem. 2000;48:1391-400 pubmed
    ..In addition, a search of the EST database revealed a related human kinase not previously described. ..
  2. 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...
  3. 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...
  4. Nugent B, Valenzuela C, Simons T, McCarthy M. Kinases SPAK and OSR1 are upregulated by estradiol and activate NKCC1 in the developing hypothalamus. J Neurosci. 2012;32:593-8 pubmed publisher
    ..of newborn rat pups significantly increases protein levels of two kinases upstream of the NKCC1 cotransporter, SPAK (STE20/SPS1-related proline alanine rich kinase) and OSR1 (oxidative stress response kinase)...
  5. 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...
  6. 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 ..
  7. 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 ..
  8. 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 ..