Gene Symbol: Stk4
Description: serine/threonine kinase 4
Alias: serine/threonine-protein kinase 4
Species: rat
Products:     Stk4

Top Publications

  1. Lee J, Kim T, Yang T, Koo B, Oh S, Lee K, et al. A crucial role of WW45 in developing epithelial tissues in the mouse. EMBO J. 2008;27:1231-42 pubmed publisher
    ..Collectively, these data provide compelling evidence that WW45 is a key mediator of MST1 signalling in the coordinate coupling of proliferation arrest with terminal differentiation for proper epithelial tissue development in mammals. ..
  2. Lehtinen M, Yuan Z, Boag P, Yang Y, Villen J, Becker E, et al. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006;125:987-1001 pubmed
  3. Graves J, Gotoh Y, Draves K, Ambrose D, Han D, Wright M, et al. Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. EMBO J. 1998;17:2224-34 pubmed
    ..Our findings suggest the existence of a positive feedback loop involving Mst1, and possibly the SAPK and p38 MAPK pathways, which serves to amplify the apoptotic response. ..
  4. Song H, Mak K, Topol L, Yun K, Hu J, Garrett L, et al. Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc Natl Acad Sci U S A. 2010;107:1431-6 pubmed publisher
  5. Creasy C, Chernoff J. Cloning and characterization of a member of the MST subfamily of Ste20-like kinases. Gene. 1995;167:303-6 pubmed
    ..The identification of MST2 suggests that there may be subfamilies of Ste20-like protein kinases and that MST1 and MST2 may define one of these subfamilies. ..
  6. Lu L, Li Y, Kim S, Bossuyt W, Liu P, Qiu Q, et al. Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver. Proc Natl Acad Sci U S A. 2010;107:1437-42 pubmed publisher
    ..Taken together, our results demonstrate that the Hippo signaling pathway is a critical regulator of mammalian liver growth and a potent suppressor of liver tumor formation. ..
  7. Chan E, Nousiainen M, Chalamalasetty R, Schäfer A, Nigg E, Sillje H. The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene. 2005;24:2076-86 pubmed
    ..Although the function of this pathway remains poorly understood in mammals, it is intriguing that, in Drosophila, it has been linked to development and tissue homeostasis. ..
  8. Cinar B, Collak F, Lopez D, Akgul S, Mukhopadhyay N, Kilicarslan M, et al. MST1 is a multifunctional caspase-independent inhibitor of androgenic signaling. Cancer Res. 2011;71:4303-13 pubmed publisher
    ..Because MST1 is also involved in regulating the AKT1 pathway, this kinase may be an important new link between androgenic and growth factor signaling and a novel therapeutic target in PCa. ..
  9. Cooper W, Hesson L, Matallanas D, Dallol A, von Kriegsheim A, Ward R, et al. RASSF2 associates with and stabilizes the proapoptotic kinase MST2. Oncogene. 2009;28:2988-98 pubmed publisher
    ..Thus, we propose that the frequent loss of RASSF2 in tumours results in the destablization of MST2 and thus decreased apoptotic potential. ..

More Information


  1. Praskova M, Xia F, Avruch J. MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Curr Biol. 2008;18:311-21 pubmed publisher
    ..MOBKL1A/MOBKL1B phosphorylation, in turn, is sufficient to inhibit proliferation through actions at several points in the cell cycle. ..
  2. Du X, Dong Y, Shi H, Li J, Kong S, Shi D, et al. Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. PLoS ONE. 2014;9:e90701 pubmed publisher
    ..Thus, our studies have defined novel roles of Mst1/2 in mouse placental development. ..
  3. Praskova M, Khoklatchev A, Ortiz Vega S, Avruch J. Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. Biochem J. 2004;381:453-62 pubmed
    ..We propose that the NORE1/RASSF1 polypeptides, in addition to their role in maintaining the low activity of MST1 in vivo, direct MST1 to sites of activation and perhaps co-localization with endogenous substrates. ..
  4. You B, Yan G, Zhang Z, Yan L, Li J, Ge Q, et al. Phosphorylation of cardiac troponin I by mammalian sterile 20-like kinase 1. Biochem J. 2009;418:93-101 pubmed publisher
    ..The results of the present study suggest that Mst1 is a novel mediator of cTnI phosphorylation in the heart and may contribute to the modulation of myofilament function under a variety of physiological and pathophysiological conditions. ..
  5. Lee K, Ohyama T, Yajima N, Tsubuki S, Yonehara S. MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation. J Biol Chem. 2001;276:19276-85 pubmed
    ..These findings suggest that MST1 and MST2 play a role in apoptosis both upstream and downstream of caspase activation. ..
  6. Hwang E, Ryu K, Pääkkönen K, Güntert P, Cheong H, Lim D, et al. Structural insight into dimeric interaction of the SARAH domains from Mst1 and RASSF family proteins in the apoptosis pathway. Proc Natl Acad Sci U S A. 2007;104:9236-41 pubmed
    ..These results imply a novel mode of interaction with RASSF family proteins and provide insight into the mechanism of apoptosis control by the SARAH domain. ..
  7. Callus B, Verhagen A, Vaux D. Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation. FEBS J. 2006;273:4264-76 pubmed
    ..Together these results show that hSav can bind to, and be phosphorylated by, Mst, and that the stabilizing effect of Mst on hSav requires its interaction with hSav but is probably not due to phosphorylation of hSav by Mst. ..
  8. Lin Y, Khokhlatchev A, Figeys D, Avruch J. Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis. J Biol Chem. 2002;277:47991-8001 pubmed
    ..MST1 is unable to directly phosphorylate p53, however, DAP4 binds endogenous and recombinant p53. DAP4 may promote MST1-induced apoptosis by enabling colocalization of MST with p53. ..
  9. Li S, Ran Y, Zhang D, Chen J, Li S, Zhu D. MicroRNA-138 plays a role in hypoxic pulmonary vascular remodelling by targeting Mst1. Biochem J. 2013;452:281-91 pubmed publisher
    ..Therefore the results of the present study suggest that miR-138 appears to be a negative regulator of PASMC apoptosis, and plays an important role in HPVR (hypoxic pulmonary vascular remodelling). ..
  10. Rawat S, Creasy C, Peterson J, Chernoff J. The tumor suppressor Mst1 promotes changes in the cellular redox state by phosphorylation and inactivation of peroxiredoxin-1 protein. J Biol Chem. 2013;288:8762-71 pubmed publisher
    ..These results suggest that hydrogen peroxide-stimulated Mst1 activates a positive feedback loop to sustain an oxidizing cellular state. ..
  11. Kawamoto Y, Ito H, Ayaki T, Takahashi R. Immunohistochemical localization of apoptosome-related proteins in Lewy bodies in Parkinson's disease and dementia with Lewy bodies. Brain Res. 2014;1571:39-48 pubmed publisher
  12. Cinar B, Fang P, Lutchman M, Di Vizio D, Adam R, Pavlova N, et al. The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1. EMBO J. 2007;26:4523-34 pubmed
    Akt kinases mediate cell growth and survival. Here, we report that a pro-apoptotic kinase, Mst1/STK4, is a physiological Akt1 interaction partner...
  13. Creasy C, Ambrose D, Chernoff J. The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain. J Biol Chem. 1996;271:21049-53 pubmed
    ..Comparison of Mst1 and Mst2 indicates that both functional domains lie in regions conserved between the two molecules. ..
  14. Yuan F, Xie Q, Wu J, Bai Y, Mao B, Dong Y, et al. MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation. J Biol Chem. 2011;286:6940-5 pubmed publisher
  15. Park B, Kim D, Won G, Jeon H, Oh B, Lee Y, et al. Mammalian ste20-like kinase and SAV1 promote 3T3-L1 adipocyte differentiation by activation of PPAR?. PLoS ONE. 2012;7:e30983 pubmed publisher
    ..These results suggest that PPAR? activation by the MST signaling pathway may be a novel regulatory mechanism of adipogenesis. ..
  16. Song H, Oh S, Oh H, Lim D. Role of the tumor suppressor RASSF2 in regulation of MST1 kinase activity. Biochem Biophys Res Commun. 2010;391:969-73 pubmed publisher
  17. Lee K, Yonehara S. Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST). J Biol Chem. 2002;277:12351-8 pubmed