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Gene Review

STK3  -  serine/threonine kinase 3

Homo sapiens

Synonyms: KRS1, MST-2, MST2, Mammalian STE20-like protein kinase 2, STE20-like kinase MST2, ...
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Disease relevance of STK3


High impact information on STK3

  • We have examined the role of caspase-mediated cleavage of the Ste20-like kinases, mammalian sterile 20-like 1 and 2 (Mst1/Mst2), in the mechanism of human eosinophil and neutrophil apoptosis [4].
  • Recently, we showed that Raf-1 kinase sequesters and inhibits MST2 and that this event is critical for Raf-mediated cell survival [5].
  • As shown previously for apoptosis induced by Ki-Ras(G12V), CNK1-induced apoptosis is suppressed by a dominant inhibitor of the mammalian sterile 20 kinases 1 and (MST1/MST2) [6].
  • Mammalian STE20-like kinase 2 (MST2), a member of the STE20-like kinase family, has been shown in previous studies to undergo proteolytic activation by caspase-3 during cell apoptosis [7].
  • A few studies have also implicated protein phosphorylation reactions in MST2 regulation [7].

Biological context of STK3


Anatomical context of STK3

  • In contrast, neutrophil apoptosis occurs independently of Mst1 and Mst2 but instead is correlated with the activation of an as-yet-unidentified 34-kd MBPK [4].
  • On the other hand, the endogenous full-length MST2 from rat thymus or from proliferating cells is mainly unphosphorylated whereas the caspase-3-truncated endogenous MST2 from apoptotic cells is highly phosphorylated [7].
  • Accordingly, we show that the mRNA and protein of the melanocyte-specific isoform of Mitf (Mitf-M) are present in several cultured CCS cell lines (Su-ccs-1, DTC1, Kao, MST-1, MST-2 and MST-3) [11].

Associations of STK3 with chemical compounds

  • MST2, therefore, mimicks, at least partially, the site by which the nicotinic acetylcholine receptor recognizes a long-chain neurotoxin [8].
  • An in vitro kinase assay indicates that MST2 can phosphorylate an exogenous substrate, as well as itself, and phospho-amino-acid analysis indicates that it is a serine/threonine protein kinase [12].
  • Borderline hypertensive but otherwise healthy 21-year-old men (n = 18) underwent 5 min of mental arithmetic stress testing (MST-1) before and at the end of 120 min of isoglycemic hyperinsulinemic glucose clamp (MST-2) with infusion rates of glucose and insulin kept constant [13].
  • The hKRS peptide also bound to DNA and polyphosphate; however, the apparent DNA-binding constants decreased at increasing concentrations of Mg(2+) [14].
  • We now show that MST2 also recognizes (-) nicotine, an agonist of AcChoR [15].

Regulatory relationships of STK3


Other interactions of STK3

  • Both are expressed predominantly as a longer (Nore1A/RASSF1A) and/or shorter (Nore1B/RASSF1C) polypeptide; all four polypeptides contain a Ras-association domain and bind, through their conserved carboxytermini, the proapoptotic protein kinases MST1 and MST2 [17].
  • The full-length phospho-MST2 is rapidly dephosphorylated by protein phosphatase 1 or protein phosphatase 2A whereas the truncated MST2 is remarkably resistant to the dephosphorylation [7].
  • In the first series (n = 18) the subjects were exposed to a 5-min mental arithmetic stress test prior to (MST-1) and at the end of (MST-2) 120 min of hyperinsulinemic glucose clamp [18].

Analytical, diagnostic and therapeutic context of STK3

  • The modified step test two (MST2) was similar to our initial MST1, except that the sandbags added every 3 min were not fixed at 1 kg but were also incremental (1, 2, 3 and 4 kg) [19].
  • The ability of the hKRS peptide to adopt alpha-helical conformation was demonstrated by NMR and circular dichroism [14].


  1. Taming the Hippo: Raf-1 controls apoptosis by suppressing MST2/Hippo. O'Neill, E., Kolch, W. Cell Cycle (2005) [Pubmed]
  2. Expression profiling of t(12;22) positive clear cell sarcoma of soft tissue cell lines reveals characteristic up-regulation of potential new marker genes including ERBB3. Schaefer, K.L., Brachwitz, K., Wai, D.H., Braun, Y., Diallo, R., Korsching, E., Eisenacher, M., Voss, R., Van Valen, F., Baer, C., Selle, B., Spahn, L., Liao, S.K., Lee, K.A., Hogendoorn, P.C., Reifenberger, G., Gabbert, H.E., Poremba, C. Cancer Res. (2004) [Pubmed]
  3. Protein A treatment of cancer: activation of a serum component with trans-species anti-B16 melanoma activity. Cooper, P.D., Masinello, G.R. Int. J. Cancer (1983) [Pubmed]
  4. Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but not neutrophil apoptosis. De Souza, P.M., Kankaanranta, H., Michael, A., Barnes, P.J., Giembycz, M.A., Lindsay, M.A. Blood (2002) [Pubmed]
  5. Mammalian sterile 20-like kinases in tumor suppression: an emerging pathway. O'Neill, E.E., Matallanas, D., Kolch, W. Cancer Res. (2005) [Pubmed]
  6. The scaffold protein CNK1 interacts with the tumor suppressor RASSF1A and augments RASSF1A-induced cell death. Rabizadeh, S., Xavier, R.J., Ishiguro, K., Bernabeortiz, J., Lopez-Ilasaca, M., Khokhlatchev, A., Mollahan, P., Pfeifer, G.P., Avruch, J., Seed, B. J. Biol. Chem. (2004) [Pubmed]
  7. Regulation of mammalian STE20-like kinase 2 (MST2) by protein phosphorylation/dephosphorylation and proteolysis. Deng, Y., Pang, A., Wang, J.H. J. Biol. Chem. (2003) [Pubmed]
  8. Recognition of the acetylcholine receptor binding site of a long-chain neurotoxin by toxin-specific monoclonal antibodies. Charpentier, I., Pillet, L., Karlsson, E., Couderc, J., Ménez, A. J. Mol. Recognit. (1990) [Pubmed]
  9. Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. O'Neill, E., Rushworth, L., Baccarini, M., Kolch, W. Science (2004) [Pubmed]
  10. The role of Krs1 in cell cycle arrest. Wang, H.C. Drug News Perspect. (2003) [Pubmed]
  11. The melanocyte inducing factor MITF is stably expressed in cell lines from human clear cell sarcoma. Li, K.K., Goodall, J., Goding, C.R., Liao, S.K., Wang, C.H., Lin, Y.C., Hiraga, H., Nojima, T., Nagashima, K., Schaefer, K.L., Lee, K.A. Br. J. Cancer (2003) [Pubmed]
  12. Cloning and characterization of a member of the MST subfamily of Ste20-like kinases. Creasy, C.L., Chernoff, J. Gene (1995) [Pubmed]
  13. Effects of hyperinsulinemia on sympathetic responses to mental stress. Høieggen, A., Fossum, E., Moan, A., Rostrup, M., Eide, I.K., Kjeldsen, S.E. Am. J. Hypertens. (2000) [Pubmed]
  14. A peptide from the extension of Lys-tRNA synthetase binds to transfer RNA and DNA. Yiadom, K.P., Hammamieh, R., Ukpabi, N., Tsang, P., Yang, D.C. Peptides (2003) [Pubmed]
  15. Anti-idiotypic and anti-anti-idiotypic responses to a monoclonal antibody directed to the acetylcholine receptor binding site of curaremimetic toxins. Pillet, L., Charpentier, I., Léonetti, M., Ménez, A. Biochim. Biophys. Acta (1992) [Pubmed]
  16. The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Chan, E.H., Nousiainen, M., Chalamalasetty, R.B., Schäfer, A., Nigg, E.A., Silljé, H.H. Oncogene (2005) [Pubmed]
  17. Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Aoyama, Y., Avruch, J., Zhang, X.F. Oncogene (2004) [Pubmed]
  18. Insulin modifies the glucose response to mental stress independently of forearm blood flow. Høieggen, A., Fossum, E., Moan, A., Eide, I.K., Kjeldsen, S.E. Blood Press. (1998) [Pubmed]
  19. Cardiovascular and respiratory adjustments in normal volunteers during modified exercise tests in comparison to standard exercise tests. Balgos, A., Lua, L., Pascual, R. Respirology (1996) [Pubmed]
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