Gene Symbol: MST
Description: serine/threonine kinase 3
Alias: 0610042I06Rik, MST, Mst2, Mst3, Ste20, mess1, serine/threonine-protein kinase 3, MST-2, STE20-like kinase MST2, mammalian STE20-like protein kinase 2, protein kinase homolog
Species: mouse
Products:     MST

Top Publications

  1. O Neill E, Rushworth L, Baccarini M, Kolch W. Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science. 2004;306:2267-70 pubmed show that Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (MST2)...
  2. Matallanas D, Romano D, Al Mulla F, O Neill E, Al Ali W, Crespo P, et al. Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras. Mol Cell. 2011;44:893-906 pubmed publisher
    ..Here, we show that mutant K-Ras directly binds to the tumor suppressor RASSF1A to activate the apoptotic MST2-LATS1 pathway...
  3. Heallen T, Zhang M, Wang J, Bonilla Claudio M, Klysik E, Johnson R, et al. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science. 2011;332:458-61 pubmed publisher
    ..Furthermore, the Hippo effector Yap interacts with β-catenin on Sox2 and Snai2 genes. These data uncover a nuclear interaction between Hippo and Wnt signaling that restricts cardiomyocyte proliferation and controls heart size. ..
  4. Wada K, Itoga K, Okano T, Yonemura S, Sasaki H. Hippo pathway regulation by cell morphology and stress fibers. Development. 2011;138:3907-14 pubmed publisher
    ..This cell morphology (stress-fiber)-mediated mechanism probably cooperates with a cell-cell contact (adhesion)-mediated mechanism involving the Hippo pathway to achieve density-dependent control of cell proliferation...
  5. Praskova M, Xia F, Avruch J. MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Curr Biol. 2008;18:311-21 pubmed publisher
    MST1 and MST2 are the mammalian Ste20-related protein kinases most closely related to Drosophila Hippo, a major regulator of cell proliferation and survival during development...
  6. Zhou D, Conrad C, Xia F, Park J, Payer B, Yin Y, et al. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell. 2009;16:425-38 pubmed publisher
    Hippo-Lats-Yorkie signaling regulates tissue overgrowth and tumorigenesis in Drosophila. We show that the Mst1 and Mst2 protein kinases, the mammalian Hippo orthologs, are cleaved and constitutively activated in the mouse liver...
  7. 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
    ..of hippo signaling in regulation of mammalian organ size we have generated conditional alleles of Sav1, mst1, and mst2, orthologs of Drosophila Salvador and hippo, respectively...
  8. George N, Day C, Boerner B, Johnson R, SARVETNICK N. Hippo signaling regulates pancreas development through inactivation of Yap. Mol Cell Biol. 2012;32:5116-28 pubmed publisher
    ..Altogether, our results demonstrate that Hippo signaling plays a crucial role in pancreas development and provide novel routes to a better understanding of pathological conditions that affect this organ. ..
  9. Choi J, Oh S, Lee D, Oh H, Park J, Lee S, et al. Mst1-FoxO signaling protects Naïve T lymphocytes from cellular oxidative stress in mice. PLoS ONE. 2009;4:e8011 pubmed publisher
    ..In C. elegans, Hippo homolog also regulates longevity. The mammalian Ste20-like protein kinase, Mst1, plays a role in apoptosis induced by various types of apoptotic stress...

More Information


  1. Mou F, Praskova M, Xia F, Van Buren D, Hock H, Avruch J, et al. The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. J Exp Med. 2012;209:741-59 pubmed publisher
    ..In this study, we analyze mice lacking both Mst1 and Mst2 in hematopoietic cells...
  2. 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
    ..We found that Mst1 and Mst2, the two mouse homologs of the Drosophila Hpo, control the sizes of some, but not all organs, in mice, and Mst1 and ..
  3. Kim S, Kim H, Koh G, Lim D, Yu D, Kim M, et al. Mouse Hepatic Tumor Vascular Imaging by Experimental Selective Angiography. PLoS ONE. 2015;10:e0131687 pubmed publisher
    ..Selective latex angiography applied to certain mouse tumor models (both ectopic and spontaneous) closely simulated typical characteristics of human HCC vascular imaging. ..
  4. Volckaert T, Yuan T, Chao C, Bell H, Sitaula A, Szimmtenings L, et al. Fgf10-Hippo Epithelial-Mesenchymal Crosstalk Maintains and Recruits Lung Basal Stem Cells. Dev Cell. 2017;43:48-59.e5 pubmed publisher
    ..Epithelial-derived Wnt7b, then in turn, induces Fgf10 expression in ASMCs, which extends the BSC niche to promote regeneration. ..
  5. Lin C, Yao E, Chuang P. A conserved MST1/2-YAP axis mediates Hippo signaling during lung growth. Dev Biol. 2015;403:101-13 pubmed publisher
    ..These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2-YAP axis in coordinating lung growth during development. ..
  6. Matsumoto H, Murakami Y, Kataoka K, Lin H, Connor K, Miller J, et al. Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment. Cell Death Dis. 2014;5:e1269 pubmed publisher
    Photoreceptor cell death is the definitive cause of vision loss in retinal detachment (RD). Mammalian STE20-like kinase (MST) is a master regulator of both cell death and proliferation and a critical factor in development and ..
  7. 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
    ..Conversely, RASSF2 activates MST1 kinase activity through formation of a RASSF2-MST1 complex, which inhibits the MST-FOXO3 signaling pathway. RASSF2 also engages the JNK pathway and induces apoptosis in an MST1-independent manner...
  8. Densham R, O Neill E, Munro J, König I, Anderson K, Kolch W, et al. MST kinases monitor actin cytoskeletal integrity and signal via c-Jun N-terminal kinase stress-activated kinase to regulate p21Waf1/Cip1 stability. Mol Cell Biol. 2009;29:6380-90 pubmed publisher
    ..We now report that the mammalian Ste20-like (MST) kinases mediate the activation of the JNK pathway in response to the disruption of the actin ..
  9. Kwan J, Sczaniecka A, Heidary Arash E, Nguyen L, Chen C, Ratkovic S, et al. DLG5 connects cell polarity and Hippo signaling protein networks by linking PAR-1 with MST1/2. Genes Dev. 2016;30:2696-2709 pubmed publisher
    ..revealed a critical role of DLG5 in the formation of protein assemblies containing core Hippo kinases mammalian ste20 homologs 1/2 (MST1/2) and Par-1 polarity proteins microtubule affinity-regulating kinases 1/2/3 (MARK1/2/3)...
  10. Maejima Y, Kyoi S, Zhai P, Liu T, Li H, Ivessa A, et al. Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2. Nat Med. 2013;19:1478-88 pubmed publisher
    ..These results suggest that Mst1 coordinately regulates autophagy and apoptosis by phosphorylating Beclin1 and consequently modulating a three-way interaction among Bcl-2 proteins, Beclin1 and Bax. ..
  11. Lee J, Youn B, Kim K, Kim J, Lee D, Seong S, et al. Mst2 Controls Bone Homeostasis by Regulating Osteoclast and Osteoblast Differentiation. J Bone Miner Res. 2015;30:1597-607 pubmed publisher
    Mammalian sterile 20-like kinase 2 (Mst2) plays a central role in the Hippo pathway, controlling cell proliferation, differentiation, and apoptosis during development...
  12. Kim W, Khan S, Gvozdenovic Jeremic J, Kim Y, Dahlman J, Kim H, et al. Hippo signaling interactions with Wnt/?-catenin and Notch signaling repress liver tumorigenesis. J Clin Invest. 2017;127:137-152 pubmed publisher
    ..Ablation of the mammalian Hippo kinases Mst1 and Mst2 in liver led to rapid HCC formation and activated Yes-associated protein/WW domain containing transcription ..
  13. Maidana D, Tsoka P, Tian B, Dib B, Matsumoto H, Kataoka K, et al. A Novel ImageJ Macro for Automated Cell Death Quantitation in the Retina. Invest Ophthalmol Vis Sci. 2015;56:6701-8 pubmed publisher
    ..We believe that this standardized measurement tool could be advantageous to compare results across different research groups, as it is freely available as open source. ..
  14. Wu H, Wei L, Fan F, Ji S, Zhang S, Geng J, et al. Integration of Hippo signalling and the unfolded protein response to restrain liver overgrowth and tumorigenesis. Nat Commun. 2015;6:6239 pubmed publisher
    ..Thus, we conclude Yap integrates Hippo and UPR signalling to control liver size and tumorigenesis. ..
  15. Su T, Bondar T, Zhou X, Zhang C, He H, Medzhitov R. Two-signal requirement for growth-promoting function of Yap in hepatocytes. elife. 2015;4: pubmed publisher
    ..These results suggest that Yap activation is insufficient to promote growth in the absence of a second signal thus coordinating tissue homeostasis and repair. ..
  16. Deng Y, Wu A, Li P, Li G, Qin L, Song H, et al. Yap1 Regulates Multiple Steps of Chondrocyte Differentiation during Skeletal Development and Bone Repair. Cell Rep. 2016;14:2224-2237 pubmed publisher
    ..Taken together, our work provides insights into the mechanism by which Yap1 regulates endochondral ossification, which may help the development of therapeutic treatment for bone regeneration. ..
  17. Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez J, Zhou D, et al. Yap1 acts downstream of ?-catenin to control epidermal proliferation. Cell. 2011;144:782-95 pubmed publisher
    ..Together, these data identify Yap1 as a determinant of the proliferative capacity of epidermal stem cells and as an important effector of a "crowd control" molecular circuitry in mammalian skin. ..
  18. Fitamant J, Kottakis F, Benhamouche S, Tian H, Chuvin N, Parachoniak C, et al. YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression. Cell Rep. 2015;: pubmed publisher
  19. Lessard Beaudoin M, Laroche M, Loudghi A, Demers M, Denault J, Grenier G, et al. Organ-specific alteration in caspase expression and STK3 proteolysis during the aging process. Neurobiol Aging. 2016;47:50-62 pubmed publisher
    ..These results further our understanding of the role of caspases and their substrates in the normal aging process and highlight a potential role for STK3 in neurodegeneration. ..
  20. Qi Q, Li D, Luo H, Guan K, Ye K. Netrin-1 exerts oncogenic activities through enhancing Yes-associated protein stability. Proc Natl Acad Sci U S A. 2015;112:7255-60 pubmed publisher
    ..decreases YAP protein levels, abrogating cancer cell progression by netrin-1, whereas knockdown of mammalian STE20-like protein kinase 1/2 (MST1/2) or large tumor suppressor kinase 1/2 (Lats1/2), two sets of upstream core kinases ..
  21. Geng J, Sun X, Wang P, Zhang S, Wang X, Wu H, et al. Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity. Nat Immunol. 2015;16:1142-52 pubmed publisher
    ..Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome ..
  22. Lee K, Yonehara S. Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST). J Biol Chem. 2002;277:12351-8 pubmed
    Mammalian STE20-like kinase (MST) is a member of the yeast STE20-related kinase family and proteolytically activated by caspase during apoptosis...
  23. Wilkinson D, Jariwala J, Anderson E, Mitra K, Meisenhelder J, Chang J, et al. Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy. Mol Cell. 2015;57:55-68 pubmed publisher
    ..Since several pathological conditions, including bacterial infections, display aberrant autophagy, we propose that pharmacological agents targeting this regulatory circuit hold therapeutic potential. ..
  24. Zhou D, Zhang Y, Wu H, Barry E, Yin Y, Lawrence E, et al. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci U S A. 2011;108:E1312-20 pubmed publisher
    Ablation of the kinases Mst1 and Mst2, orthologs of the Drosophila antiproliferative kinase Hippo, from mouse intestinal epithelium caused marked expansion of an undifferentiated stem cell compartment and loss of secretory cells ..
  25. Heallen T, Morikawa Y, Leach J, Tao G, Willerson J, Johnson R, et al. Hippo signaling impedes adult heart regeneration. Development. 2013;140:4683-90 pubmed publisher
    ..Our findings reveal that Hippo signaling is an endogenous repressor of adult cardiomyocyte renewal and regeneration. Targeting the Hippo pathway in human disease might be beneficial for the treatment of heart disease. ..
  26. Li W, Xiao J, Zhou X, Xu M, Hu C, Xu X, et al. STK4 regulates TLR pathways and protects against chronic inflammation-related hepatocellular carcinoma. J Clin Invest. 2015;125:4239-54 pubmed publisher
    ..Together, our results suggest that STK4 has potential as a diagnostic biomarker and therapeutic target for inflammation-induced HCC. ..
  27. Oh H, Kim M, Song S, Kim T, Lee D, Kwon S, et al. MST1 limits the kinase activity of aurora B to promote stable kinetochore-microtubule attachment. Curr Biol. 2010;20:416-22 pubmed publisher
    ..MST1 is thus a key regulator of Aurora B activity that ensures mitotic chromosome congression and accurate chromosome segregation. ..
  28. Du X, Shi H, Li J, Dong Y, Liang J, Ye J, et al. Mst1/Mst2 regulate development and function of regulatory T cells through modulation of Foxo1/Foxo3 stability in autoimmune disease. J Immunol. 2014;192:1525-35 pubmed publisher
    ..Finally, we demonstrate that Mst1 and Mst2 play a partially redundant role in Treg development and autoimmunity...
  29. Sasaki H. Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos. Semin Cell Dev Biol. 2015;47-48:80-7 pubmed publisher
    ..In this review, I discuss how these mechanisms cooperate with the Hippo signaling pathway during cell fate-specification processes. ..
  30. Loforese G, Malinka T, Keogh A, Baier F, Simillion C, Montani M, et al. Impaired liver regeneration in aged mice can be rescued by silencing Hippo core kinases MST1 and MST2. EMBO Mol Med. 2017;9:46-60 pubmed publisher
    ..We provide pre-clinical evidence that silencing the Hippo core kinases MST1 and MST2 with siRNA provokes hepatocyte proliferation in quiescent livers and rescues liver regeneration in aged mice ..
  31. Kondo N, Ueda Y, Kita T, Ozawa M, Tomiyama T, Yasuda K, et al. NDR1-Dependent Regulation of Kindlin-3 Controls High-Affinity LFA-1 Binding and Immune Synapse Organization. Mol Cell Biol. 2017;37: pubmed publisher
    ..Rap1 was essential for T cell attachment, whereas deficiencies of ste20-like kinases, Mst1/Mst2, diminished high-affinity binding and abrogated central SMAC (cSMAC) formation with ..
  32. Hu J, Du W, Shelton S, Oldham M, DiPersio C, Klein O. An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice. Cell Stem Cell. 2017;21:91-106.e6 pubmed publisher
    ..This leads to Rheb expression and potentiates mTOR signaling to drive the proliferation of TA cells. These findings thus reveal a YAP/TAZ signaling mechanism that coordinates stem cell expansion and differentiation during organ renewal. ..
  33. 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
    The human serine/threonine kinase, mammalian STE20-like kinase (MST), is considerably homologous to the budding yeast kinases, SPS1 and STE20, throughout their kinase domains...
  34. Lee G, Yan L, Vatner D, Vatner S. Mst1 inhibition rescues β1-adrenergic cardiomyopathy by reducing myocyte necrosis and non-myocyte apoptosis rather than myocyte apoptosis. Basic Res Cardiol. 2015;110:7 pubmed publisher
    ..However, this did not occur through Mst1 inhibition of myocyte apoptosis but rather by inhibition of cardiomyocyte necrosis and non-myocyte apoptosis, features of Mst1 not considered previously. ..
  35. 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
    The mammalian ste20 kinase (MST) signaling pathway plays an important role in the regulation of apoptosis and cell cycle control...
  36. Zi M, Maqsood A, Prehar S, Mohamed T, Abou Leisa R, Robertson A, et al. The mammalian Ste20-like kinase 2 (Mst2) modulates stress-induced cardiac hypertrophy. J Biol Chem. 2014;289:24275-88 pubmed publisher
    ..However, its role in the adult heart is incompletely understood. We investigate here the role of mammalian Ste20-like kinase 2 (Mst2), one of the central regulators of this pathway...
  37. Oka T, Mazack V, Sudol M. Mst2 and Lats kinases regulate apoptotic function of Yes kinase-associated protein (YAP). J Biol Chem. 2008;283:27534-46 pubmed publisher
    ..These kinases cooperate with the upstream Mst2 kinase to phosphorylate YAPs at Ser-127...
  38. Gao T, Zhou D, Yang C, Singh T, Penzo Méndez A, Maddipati R, et al. Hippo signaling regulates differentiation and maintenance in the exocrine pancreas. Gastroenterology. 2013;144:1543-53, 1553.e1 pubmed publisher
    ..In this study, we investigated the role of the core Hippo kinases-Mst1 and Mst2-in pancreatic development and homeostasis...
  39. Li P, Chen Y, Mak K, Wong C, Wang C, Yuan P. Functional role of Mst1/Mst2 in embryonic stem cell differentiation. PLoS ONE. 2013;8:e79867 pubmed publisher
    ..Mst1 and Mst2 are central components of this pathway that are essential for embryonic development, though their role in ..
  40. Reginensi A, Scott R, Gregorieff A, Bagherie Lachidan M, Chung C, Lim D, et al. Yap- and Cdc42-dependent nephrogenesis and morphogenesis during mouse kidney development. PLoS Genet. 2013;9:e1003380 pubmed publisher
    ..We propose that Yap responds to Cdc42-dependent signals in nephron progenitor cells to activate a genetic program required to shape the functioning nephron. ..
  41. 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
    ..Mst1 and Mst2 (Mst1/2), key components of the mammalian hpo/Mst signaling pathway, encode two highly conserved Ser/Thr kinases ..