The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

STK39  -  serine threonine kinase 39

Homo sapiens

Synonyms: DCHT, PASK, SPAK, STE20/SPS1-related proline-alanine-rich protein kinase, Serine/threonine-protein kinase 39, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of STK39


High impact information on STK39

  • The magnitude and duration of TCR/CD28-induced endogenous SPAK activation were markedly impaired in PKCtheta-deficient T cells [2].
  • WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1 [3].
  • Suppression of UV-induced K+ channel activation with specific channel blockers prevented UV-induced apoptosis through inhibition of UV-induced activation of the proteins SEK (SPAK kinase) and JNK [4].
  • MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway [5].
  • SPAK (STE20/SPS1-related, proline alanine-rich kinase) belongs to the SPS1 subfamily of STE20 kinases and is highly conserved between species [6].

Biological context of STK39

  • Here we have shown that WNK1 phosphorylates and regulates the STE20-related kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1) [3].
  • The residues on NKCC1, phosphorylated by SPAK/OSR1, are conserved in other cation co-transporters, such as the Na+-Cl- co-transporter, the target of thiazide drugs that lower blood pressure in humans with Gordon's syndrome [7].
  • Genetic analysis suggests that OSR1 evolved first, with SPAK arising following a gene duplication in vertebrate evolution [8].
  • SPAK and OSR1 are two recently discovered kinases which have been linked to several key cellular processes, including cell differentiation, cell transformation and proliferation, cytoskeleton rearrangement, and most recently, regulation of ion transporters [8].
  • Based on the alignment of 12 sequences of protein motifs that interact with the kinases SPAK (Ste20-related proline alanine-rich kinase) and OSR1 (oxidative stress response 1), we performed genome-wide searches of the sequence [S/G/V]RFx[V/I]xx[V/I/T/S]xx, where x represents any amino acid [9].

Anatomical context of STK39

  • SPAK is expressed ubiquitously, although preferentially in brain and pancreas [6].
  • We immunoprecipitated WNK1 from extracts of rat testis and found that it was specifically associated with a protein kinase of the STE20 family termed 'STE20/SPS1-related proline/alanine-rich kinase' (SPAK) [10].
  • In addition, TRAIL reduced the activity of SPAK in HeLa cells in a caspase-independent manner [11].

Associations of STK39 with chemical compounds


Physical interactions of STK39

  • Using a yeast two-hybrid system, we identified a Ste20-related proline-alanine-rich kinase (SPAK) that binds RELT [13].

Regulatory relationships of STK39

  • These findings suggest that WNK isoforms operate as protein kinases that activate SPAK and OSR1 by phosphorylating the T-loops of these enzymes, resulting in their activation [10].

Other interactions of STK39

  • In addition, a kinase-dead SPAK acted as an inhibitor of RELT signaling [13].
  • We report here that SPAK, a recently identified STE20/SPS1-related kinase that modulates p38 MAP kinase activity, exhibited increased expression in androgen-treated LNCaP cells [1].
  • R1881-induced SPAK expression was completely abrogated by the antiandrogen casodex and by actinomycin D indicating that androgen induction of SPAK requires the androgen receptor and transcription [1].
  • Using recombinant proteins, we demonstrate direct binding of PKCdelta to SPAK, PKCdelta-mediated activation of SPAK, binding of SPAK to the amino terminus of NKCC1 (NT-NKCC1, amino acids 1-286), and competitive inhibition of SPAK-NKCC1 binding by a peptide encoding a SPAK binding site on NT-NKCC1 [14].

Analytical, diagnostic and therapeutic context of STK39

  • First, Western blot analysis revealed the presence, and in some tissues abundance, of truncated forms of SPAK and OSR1 in which the kinase domains are affected and thus lack kinase activity [15].


  1. Androgens induce expression of SPAK, a STE20/SPS1-related kinase, in LNCaP human prostate cancer cells. Qi, H., Labrie, Y., Grenier, J., Fournier, A., Fillion, C., Labrie, C. Mol. Cell. Endocrinol. (2001) [Pubmed]
  2. SPAK kinase is a substrate and target of PKCtheta in T-cell receptor-induced AP-1 activation pathway. Li, Y., Hu, J., Vita, R., Sun, B., Tabata, H., Altman, A. EMBO J. (2004) [Pubmed]
  3. WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1. Moriguchi, T., Urushiyama, S., Hisamoto, N., Iemura, S., Uchida, S., Natsume, T., Matsumoto, K., Shibuya, H. J. Biol. Chem. (2005) [Pubmed]
  4. An ultraviolet-activated K+ channel mediates apoptosis of myeloblastic leukemia cells. Wang, L., Xu, D., Dai, W., Lu, L. J. Biol. Chem. (1999) [Pubmed]
  5. MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway. Lin, J.L., Chen, H.C., Fang, H.I., Robinson, D., Kung, H.J., Shih, H.M. Oncogene (2001) [Pubmed]
  6. SPAK, a STE20/SPS1-related kinase that activates the p38 pathway. Johnston, A.M., Naselli, G., Gonez, L.J., Martin, R.M., Harrison, L.C., DeAizpurua, H.J. Oncogene (2000) [Pubmed]
  7. Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1. Vitari, A.C., Thastrup, J., Rafiqi, F.H., Deak, M., Morrice, N.A., Karlsson, H.K., Alessi, D.R. Biochem. J. (2006) [Pubmed]
  8. SPAK and OSR1, key kinases involved in the regulation of chloride transport. Delpire, E., Gagnon, K.B. Acta physiologica (Oxford, England) (2006) [Pubmed]
  9. Genome-wide analysis of SPAK/OSR1 binding motifs. Delpire, E., Gagnon, K.B. Physiol. Genomics (2007) [Pubmed]
  10. The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases. Vitari, A.C., Deak, M., Morrice, N.A., Alessi, D.R. Biochem. J. (2005) [Pubmed]
  11. TRAIL-induced cleavage and inactivation of SPAK sensitizes cells to apoptosis. Polek, T.C., Talpaz, M., Spivak-Kroizman, T.R. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  12. Regulatory phosphorylation sites in the NH2 terminus of the renal Na-K-Cl cotransporter (NKCC2). Giménez, I., Forbush, B. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  13. The TNF receptor, RELT, binds SPAK and uses it to mediate p38 and JNK activation. Polek, T.C., Talpaz, M., Spivak-Kroizman, T. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  14. PKCdelta acts upstream of SPAK in the activation of NKCC1 by hyperosmotic stress in human airway epithelial cells. Smith, L., Smallwood, N., Altman, A., Liedtke, C.M. J. Biol. Chem. (2008) [Pubmed]
  15. 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. Piechotta, K., Garbarini, N., England, R., Delpire, E. J. Biol. Chem. (2003) [Pubmed]
WikiGenes - Universities