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Gene Review

STK4  -  serine/threonine kinase 4

Homo sapiens

Synonyms: KRS2, MST-1, MST1, Mammalian STE20-like protein kinase 1, STE20-like kinase MST1, ...
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Disease relevance of STK4


High impact information on STK4


Biological context of STK4

  • These studies therefore implicate a role for caspase- and H(2)O(2)-mediated cleavage of the Mst1 and the subsequent release of the 36-kd catalytic fragment in the mechanism of eosinophil apoptosis [6].
  • Moreover, MST1 polypeptides, bound via wild-type NORE1A to Ras(G12V) (where G12V stands for Gly12Val), exhibit higher Thr183 phosphorylation compared with MST1 bound to NORE1A alone [7].
  • Mst1 may therefore represent an important target for caspases during cell death which serves to amplify the apoptotic response [1].
  • Nore1 and RASSF1 Regulation of Cell Proliferation and of the MST1/2 Kinases [8].
  • Our study demonstrates a previously unknown function for Mst1 of relaying the Rap1-RAPL signal to induce cell polarity and adhesion of lymphocytes [3].

Anatomical context of STK4


Associations of STK4 with chemical compounds

  • Autophosphorylation of Mst1 on a serine residue close to one of the caspase sites inhibited caspase-mediated cleavage in vitro [1].
  • Mammalian Sterile20-like kinase 1 (Mst1) is a ubiquitously expressed serine/threonine kinase which represents a member of the rapidly expanding family of enzymes related to the yeast Sterile20 kinase [11].
  • In conclusion, our study not only confirms that MST1, glutathione S-transferase p1-1, glycoprotein IX and soluble PPase belong to MAPK pathways, but also provides seven novel molecules for the further study of the pathways [12].
  • Knockdown of MST1 expression by small interfering RNA diminished bortezomib-induced apoptosis or caspase-3 activation [13].

Regulatory relationships of STK4

  • Moreover, the stimulatory effect of RASSF1A overexpression on Fas-induced apoptosis was inhibited by depletion of Mst1 [9].

Other interactions of STK4

  • Finally, Mst1 appears to function upstream of the protein kinase MEKK1 in the SAPK pathway [1].
  • Here we have identified the kinase Mst1 as a critical effector of RAPL [3].
  • Hpo most closely resembles the pro-apoptotic mammalian sterile20 kinases 1 and 2 (Mst1 and 2), and Salvador (Sav) has a human orthologue hSav (also called hWW45) [14].

Analytical, diagnostic and therapeutic context of STK4


  1. Both phosphorylation and caspase-mediated cleavage contribute to regulation of the Ste20-like protein kinase Mst1 during CD95/Fas-induced apoptosis. Graves, J.D., Draves, K.E., Gotoh, Y., Krebs, E.G., Clark, E.A. J. Biol. Chem. (2001) [Pubmed]
  2. Homozygous deletion of the p16/MTS-1/CDKN2 gene in malignant gliomas is infrequent among Japanese patients. Mochizuki, S., Iwadate, Y., Namba, H., Yoshida, Y., Yamaura, A., Sakiyama, S., Tagawa, M. Int. J. Oncol. (1999) [Pubmed]
  3. Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. Katagiri, K., Imamura, M., Kinashi, T. Nat. Immunol. (2006) [Pubmed]
  4. Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. Graves, J.D., Gotoh, Y., Draves, K.E., Ambrose, D., Han, D.K., Wright, M., Chernoff, J., Clark, E.A., Krebs, E.G. EMBO J. (1998) [Pubmed]
  5. Regulation of NDR protein kinase by hydrophobic motif phosphorylation mediated by the mammalian Ste20-like kinase MST3. Stegert, M.R., Hergovich, A., Tamaskovic, R., Bichsel, S.J., Hemmings, B.A. Mol. Cell. Biol. (2005) [Pubmed]
  6. 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]
  7. Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. Praskova, M., Khoklatchev, A., Ortiz-Vega, S., Avruch, J. Biochem. J. (2004) [Pubmed]
  8. Nore1 and RASSF1 Regulation of Cell Proliferation and of the MST1/2 Kinases. Avruch, J., Praskova, M., Ortiz-Vega, S., Liu, M., Zhang, X.F. Meth. Enzymol. (2005) [Pubmed]
  9. Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis. Oh, H.J., Lee, K.K., Song, S.J., Jin, M.S., Song, M.S., Lee, J.H., Im, C.R., Lee, J.O., Yonehara, S., Lim, D.S. Cancer Res. (2006) [Pubmed]
  10. 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]
  11. Mammalian Sterile20-like kinase 1 and the regulation of apoptosis. de Souza, P.M., Lindsay, M.A. Biochem. Soc. Trans. (2004) [Pubmed]
  12. Proteomic approach to substrates related to MAPK pathway in 293T cells. Zhang, G., Wang, S. Cell Biol. Int. (2007) [Pubmed]
  13. Activation of sterile20-like kinase 1 in proteasome inhibitor bortezomib-induced apoptosis in oncogenic K-ras-transformed cells. Teraishi, F., Guo, W., Zhang, L., Dong, F., Davis, J.J., Sasazuki, T., Shirasawa, S., Liu, J., Fang, B. Cancer Res. (2006) [Pubmed]
  14. Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation. Callus, B.A., Verhagen, A.M., Vaux, D.L. FEBS J. (2006) [Pubmed]
  15. The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain. Creasy, C.L., Ambrose, D.M., Chernoff, J. J. Biol. Chem. (1996) [Pubmed]
  16. 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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