STK3

Summary

Gene Symbol: STK3
Description: serine/threonine kinase 3
Alias: KRS1, MST2, serine/threonine-protein kinase 3, KB-1458E12.1, MST-2, STE20-like kinase MST2, mammalian STE20-like protein kinase 2, serine/threonine kinase 3 (STE20 homolog, yeast), serine/threonine kinase 3 (Ste20, yeast homolog), serine/threonine-protein kinase Krs-1
Species: human
Products:     STK3

Top Publications

  1. Creasy C, Chernoff J. Cloning and characterization of a human protein kinase with homology to Ste20. J Biol Chem. 1995;270:21695-700 pubmed
    ..Thus MST1, although homologous to a member of a yeast MAPK cascade, is not involved in the regulation of a known mammalian MAPK pathway and potentially regulates a novel signaling cascade. ..
  2. 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
    ..In this study, we show that MST1 and MST2 are direct substrates of caspase-3 both in vivo and in vitro...
  3. De Souza P, Kankaanranta H, Michael A, Barnes P, Giembycz M, Lindsay M. Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but not neutrophil apoptosis. Blood. 2002;99:3432-8 pubmed
    ..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. 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
    MST1 (mammalian Sterile20-like 1) and MST2 are closely related Class II GC (protein Ser/Thr) kinases that initiate apoptosis when transiently overexpressed in mammalian cells...
  5. 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
    ..to show that Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (MST2)...
  6. 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
    ..Little, however, is known about the function and regulation of human Lats kinases. Here we report that human Mst2, a STE20-family member and purported Hpo ortholog, phosphorylates and activates both Lats1 and Lats2...
  7. Matallanas D, Romano D, Yee K, Meissl K, Kucerova L, Piazzolla D, et al. RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Mol Cell. 2007;27:962-75 pubmed
    ..Apoptosis can be driven by either activating Bax or by activation of MST kinases. The Raf1 proto-oncogene binds to MST2, preventing its activation and proapoptotic signaling...
  8. Ikeda M, Kawata A, Nishikawa M, Tateishi Y, Yamaguchi M, Nakagawa K, et al. Hippo pathway-dependent and -independent roles of RASSF6. Sci Signal. 2009;2:ra59 pubmed publisher
    ..Here, we characterize the interaction between MST2 and another mammalian RASSF isoform, RASSF6...
  9. Kim D, Shu S, Coppola M, Kaneko S, Yuan Z, Cheng J. Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway. PLoS ONE. 2010;5:e9616 pubmed publisher
    ..Its mammalian homolog MST2 has been shown to play similar role and be regulated by Raf-1 via a kinase-independent mechanism and by RASSF ..

More Information

Publications128 found, 100 shown here

  1. Creasy C, Chernoff J. Cloning and characterization of a member of the MST subfamily of Ste20-like kinases. Gene. 1995;167:303-6 pubmed
    We have identified a second human homology of the yeast Ste20 protein kinase family, which we designate MST2. MST2 is most similar to the previously identified MST1 protein kinase (78% identity, 88% similarity)...
  2. Taylor L, Wang H, Erikson R. Newly identified stress-responsive protein kinases, Krs-1 and Krs-2. Proc Natl Acad Sci U S A. 1996;93:10099-104 pubmed
    ..The specificity of Krs-1 and Krs-2 activation and their similarity to Ste20p suggest that they may function at an early step in phosphorylation events that are specific responses to some forms of chemical stress or extreme heat shock. ..
  3. Oh H, Lee K, Song S, Jin M, Song M, Lee J, et al. Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis. Cancer Res. 2006;66:2562-9 pubmed
    ..These findings indicate that RASSF1A facilitates Mst1 activation and thereby promotes apoptosis induced by death receptor signaling. ..
  4. Guo C, Tommasi S, Liu L, Yee J, Dammann R, Pfeifer G. RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network. Curr Biol. 2007;17:700-5 pubmed
    ..work in Drosophila has led to the discovery of a new tumor-suppressor pathway involving the Drosophila MST1 and MST2 ortholog, Hippo, as well as the Lats/Warts serine/threonine kinase and a protein named Salvador (Sav)...
  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. Romano D, Matallanas D, Weitsman G, Preisinger C, Ng T, Kolch W. Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A, Raf-1, and Akt. Cancer Res. 2010;70:1195-203 pubmed publisher
    ..However, there is limited understanding about MST2 control by key regulators of cell division and survival...
  7. Kumar A, Greggio E, Beilina A, Kaganovich A, Chan D, Taymans J, et al. The Parkinson's disease associated LRRK2 exhibits weaker in vitro phosphorylation of 4E-BP compared to autophosphorylation. PLoS ONE. 2010;5:e8730 pubmed publisher
    ..We also tested three other kinases (STK3, MAPK14/p38alpha and DAPK2) and found that MAPK14/p38alpha could efficiently phosphorylate 4E-BP at the same site ..
  8. Sang B, Zhang Y, Guo S, Kong L, Cheng Q, Liu G, et al. Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence. Proc Natl Acad Sci U S A. 2018;115:E11661-E11670 pubmed publisher
    ..Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1...
  9. Turunen S, von Nandelstadh P, Ohman T, Gucciardo E, Seashore Ludlow B, Martins B, et al. FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2-dependent apoptosis. Cell Death Differ. 2019;: pubmed publisher
    ..Using a kinase substrate screen, we identified here MST1 and MST2 among the top substrates for fibroblast growth factor receptor 4 (FGFR4)...
  10. Blaszczyk K, Olejnik A, Nowicka H, Ozgyin L, Chen Y, Chmielewski S, et al. STAT2/IRF9 directs a prolonged ISGF3-like transcriptional response and antiviral activity in the absence of STAT1. Biochem J. 2015;466:511-24 pubmed publisher
    ..human STAT2 (hST2-U3C) and STAT1-deficient murine embryonic fibroblast cells stably overexpressing mouse STAT2 (mST2-MS1KO) we observed that the IFNα-induced expression of 2'-5'-oligoadenylate synthase 2 (OAS2) and interferon-..
  11. Zhang J, Ramadan A, Griesenauer B, Li W, Turner M, Liu C, et al. ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease. Sci Transl Med. 2015;7:308ra160 pubmed publisher
    ..sST2 sequesters interleukin-33 (IL-33), limiting its availability to T cells expressing membrane-bound ST2 (mST2) [T helper 2 (TH2) cells and ST2(+)FoxP3(+) regulatory T cells]...
  12. Baragaña B, Forte B, Choi R, Nakazawa Hewitt S, Bueren Calabuig J, Pisco J, et al. Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis. Proc Natl Acad Sci U S A. 2019;116:7015-7020 pubmed publisher
    ..Target deconvolution in P. falciparum has shown that cladosporin inhibits lysyl-tRNA synthetase (PfKRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs...
  13. Wang P, Geng J, Gao J, Zhao H, Li J, Shi Y, et al. Macrophage achieves self-protection against oxidative stress-induced ageing through the Mst-Nrf2 axis. Nat Commun. 2019;10:755 pubmed publisher
    ..Here we show that the kinases Mst1 and Mst2 (Mst1/2) sense ROS and maintain cellular redox balance by modulating the stability of antioxidant transcription ..
  14. 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...
  15. Karchugina S, Chernoff J. Detection of Heterodimerization of Protein Isoforms Using an in Situ Proximity Ligation Assay. J Vis Exp. 2018;: pubmed publisher
    ..In this presentation, we show how to apply the PLA technique to visualize changes in MST1 and MST2 proximity in fixed cells...
  16. Ni L, Luo X. Structural and Biochemical Analyses of the Core Components of the Hippo Pathway. Methods Mol Biol. 2019;1893:239-256 pubmed publisher
    ..Here we describe the detailed methods for the purification and crystallization of the MST2-SAV1 and pMOB1-LATS1 complexes, for assaying the SAV1-dependent inhibition of PP2A, and for analyzing LATS1 kinase ..
  17. 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
    ..Here, we report that LC3 is phosphorylated at threonine 50 (Thr(50)) by the mammalian Sterile-20 kinases STK3 and STK4...
  18. Storey A, Wang H, Protacio R, Davidson M, Tackett A, Wahls W. Chromatin-mediated regulators of meiotic recombination revealed by proteomics of a recombination hotspot. Epigenetics Chromatin. 2018;11:64 pubmed publisher
    ..Proteins and PTMs enriched at the hotspot included known regulators (Atf1, Pcr1, Mst2, Snf22, H3K14ac), validating the approach...
  19. Pefani D, Tognoli M, Pirincci Ercan D, Gorgoulis V, O Neill E. MST2 kinase suppresses rDNA transcription in response to DNA damage by phosphorylating nucleolar histone H2B. EMBO J. 2018;37: pubmed publisher
    ..We identified that the MST2 kinase localises at the nucleoli and targets phosphorylation of H2BS14p in an ATM-dependent manner...
  20. Xiong S, Couzens A, Kean M, Mao D, Guettler S, Kurinov I, et al. Regulation of Protein Interactions by Mps One Binder (MOB1) Phosphorylation. Mol Cell Proteomics. 2017;16:1111-1125 pubmed publisher
    ..Human MOB1 binds both the upstream kinases MST1 and MST2 and the downstream AGC group kinases LATS1, LATS2, NDR1, and NDR2...
  21. Shi H, Liu C, Tan H, Li Y, Nguyen T, Dhungana Y, et al. Hippo Kinases Mst1 and Mst2 Sense and Amplify IL-2R-STAT5 Signaling in Regulatory T Cells to Establish Stable Regulatory Activity. Immunity. 2018;49:899-914.e6 pubmed publisher
    ..High Mst1 and Mst2 (Mst1-Mst2) activity in Treg cells was crucial to prevent tumor resistance and autoimmunity...
  22. Xu F, Wang Y, Chang J, Du S, Diao L, Jiang N, et al. Mammalian sterile 20-like kinase 1/2 inhibits the Wnt/?-catenin signalling pathway by directly binding casein kinase 1?. Biochem J. 2014;458:159-69 pubmed publisher
    ..Moreover, MST2, the close homologue of MST1, also displayed the similar function in suppressing the Wnt/?-catenin pathway...
  23. Lange A, Sridharan A, Xu Y, Stripp B, Perl A, Whitsett J. Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung. J Mol Cell Biol. 2015;7:35-47 pubmed publisher
    ..To determine the role of Hippo signaling in the lung, the mammalian Hippo kinases, Mst1 and Mst2, were deleted in epithelial cells of the embryonic and mature mouse lung...
  24. Wermke M, Camgoz A, Paszkowski Rogacz M, Thieme S, von Bonin M, Dahl A, et al. RNAi profiling of primary human AML cells identifies ROCK1 as a therapeutic target and nominates fasudil as an antileukemic drug. Blood. 2015;125:3760-8 pubmed publisher
    ..Stringent validation identified 6 genes (BNIPL1, ROCK1, RPS13, STK3, SNX27, WDHD1) whose knockdown impaired growth and viability of the cells...
  25. Oristian K, Crose L, Kuprasertkul N, Bentley R, Lin Y, Williams N, et al. Loss of MST/Hippo Signaling in a Genetically Engineered Mouse Model of Fusion-Positive Rhabdomyosarcoma Accelerates Tumorigenesis. Cancer Res. 2018;78:5513-5520 pubmed publisher
    ..To this end, MST1/2-floxed (Stk3F/F;Stk4F/F ) mice were crossed with a previously established aRMS GEMM driven by ..
  26. Hong L, Li Y, Liu Q, Chen Q, Chen L, Zhou D. The Hippo Signaling Pathway in Regenerative Medicine. Methods Mol Biol. 2019;1893:353-370 pubmed publisher
    ..We and others have demonstrated that the genetic disruption of kinases Mst1 and Mst2 (Mst1/2), the core components of Hippo signaling, results in YAP activation and sustained liver growth, thereby ..
  27. 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 mislocalized kindlin-3 and ..
  28. Romano D, Matallanas D, Frederick D, Flaherty K, Kolch W. One Hippo and many masters: differential regulation of the Hippo pathway in cancer. Biochem Soc Trans. 2014;42:816-21 pubmed publisher
    The Hippo/MST2 (mammalian sterile 20-like kinase 2) pathway is a signalling cascade evolutionarily conserved in its structure...
  29. Wang J, Reddy B, Jia S. Rapid epigenetic adaptation to uncontrolled heterochromatin spreading. elife. 2015;4: pubmed publisher
    ..In this study, we show that the conserved Mst2 histone acetyltransferase complex in fission yeast regulates histone turnover at heterochromatin regions to control ..
  30. Pefani D, O Neill E. Safeguarding genome stability: RASSF1A tumor suppressor regulates BRCA2 at stalled forks. Cell Cycle. 2015;14:1624-30 pubmed publisher
    ..Recently we uncovered how the core Hippo pathway components RASSF1A, MST2 and LATS1 regulate CDK2 activity towards BRCA2, in response to fork stalling...
  31. 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 ..
  32. Patel S, Camargo F, Yimlamai D. Hippo Signaling in the Liver Regulates Organ Size, Cell Fate, and Carcinogenesis. Gastroenterology. 2017;152:533-545 pubmed publisher
    ..The pathway takes its name from the Drosophila protein kinase, Hippo (STK4/MST1 and STK3/MST2 in mammals), which, when inactivated, leads to considerable tissue overgrowth...
  33. Wang J, Cai Q, Qiu L, Ying S, Feng M. The histone acetyltransferase Mst2 sustains the biological control potential of a fungal insect pathogen through transcriptional regulation. Appl Microbiol Biotechnol. 2018;102:1343-1355 pubmed publisher
    ..Here, we show the functions of a histone acetyltransferase that is phylogenetically close to Mst2 in fission yeast and specifically acetylates histone H3K14 in Beauveria bassiana, a fungal insect pathogen widely ..
  34. Bae S, Ni L, Osinski A, Tomchick D, Brautigam C, Luo X. SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK. elife. 2017;6: pubmed publisher
    ..SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop...
  35. Du X, Wen J, Wang Y, Karmaus P, Khatamian A, Tan H, et al. Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells. Nature. 2018;558:141-145 pubmed publisher
    ..we use a data-driven systems biology algorithm (NetBID) to identify a role of the Hippo pathway kinases Mst1 and Mst2 (Mst1/2) in selectively programming CD8α+ dendritic cell function and metabolism...
  36. Lee D, Kim T, Lee D, Lim D. Mammalian sterile 20 kinase 1 and 2 are important regulators of hematopoietic stem cells in stress condition. Sci Rep. 2018;8:942 pubmed publisher
    ..MST1 and MST2 (MST1/2) are core serine-threonine kinases in the Hippo signaling pathway, one of which, MST1, has been extensively ..
  37. Chu P, He L, Xiong L, Luo L, Huang R, Liao L, et al. Molecular cloning, expression analysis and localization pattern of the MST family in grass carp (Ctenopharyngodon idella). Fish Shellfish Immunol. 2018;76:316-323 pubmed publisher
    ..the serine/threonine protein kinase superfamily, has five members that can be found in mammals: STK3 (also called MST2), STK4 (MST1), STK24 (MST3), STK25 (YSK1 or SOK1), and STK26 (MST4)...
  38. Park Y, Park J, Lee Y, Lim W, Oh B, Shin C, et al. Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand. J Mol Med (Berl). 2011;89:181-91 pubmed publisher
    Mammalian MST2 kinase plays an important role in cell proliferation, survival, and apoptosis...
  39. Jolivet E, Plavonil C, Sainte Rose M, Schaub B. [Assessment of screening for Down syndrome in Martinique from 2011 to 2013: An island location favoured]. J Gynecol Obstet Biol Reprod (Paris). 2016;45:1159-1164 pubmed publisher
    ..6 % on a sequential calculation of risk (CRS) and 10.8 % on serum markers 2nd trimester (MST2). Overall 5.4 % of the patients were placed in a risk group...
  40. Cairns L, Tran T, Fowl B, Patterson A, Kim Y, Bothner B, et al. Salvador has an extended SARAH domain that mediates binding to Hippo kinase. J Biol Chem. 2018;293:5532-5543 pubmed publisher
    ..Of note, Salvador influenced the kinase activity of Mst2, the mammalian Hippo homolog...
  41. 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 ..
  42. Varelas X, Miller B, Sopko R, Song S, Gregorieff A, Fellouse F, et al. The Hippo pathway regulates Wnt/beta-catenin signaling. Dev Cell. 2010;18:579-91 pubmed publisher
    ..These results uncover a cytoplasmic function of TAZ in regulating Wnt signaling and highlight the role of the Hippo pathway in coordinating morphogenetic signaling with growth control. ..
  43. Yuan H, Liu H, Liu Z, Zhu D, Amos C, Fang S, et al. Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival. Int J Cancer. 2015;137:638-45 pubmed publisher
    ..e., MST1, MST2, SAV1, LATS1, LATS2, MOB1A, MOB1B, YAP1, TEAD1, TEAD2, TEAD3 and TEAD4) from the dataset of our previously ..
  44. Zhang X, Guo C, Wu X, Li A, Liu L, Tsark W, et al. Analysis of Liver Tumor-Prone Mouse Models of the Hippo Kinase Scaffold Proteins RASSF1A and SAV1. Cancer Res. 2016;76:2824-35 pubmed publisher
    ..As a binding partner of the kinases MST1 and MST2, the mammalian orthologs of the Drosophila Hippo kinase, RASSF1A is a potential regulator of the Hippo tumor ..
  45. Tang R, Lei Y, Hu B, Yang J, Fang S, Wang Q, et al. WW domain binding protein 5 induces multidrug resistance of small cell lung cancer under the regulation of miR-335 through the Hippo pathway. Br J Cancer. 2016;115:243-51 pubmed publisher
    ..We also conducted western blot to detect the expression of MST2 and YAP1 and their phosphorylated protein...
  46. 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
    ..As the serine/threonine kinase family is involved in apoptosis and serine/threonine kinase 3 (STK3) is a recently identified caspase-6 substrate, we assessed the expression and cleavage of STK3 in murine peripheral ..
  47. Thompson B, Sahai E. MST kinases in development and disease. J Cell Biol. 2015;210:871-82 pubmed publisher
    ..is related to the Hippo kinase in Drosophila melanogaster, includes five related proteins: MST1 (also called STK4), MST2 (also called STK3), MST3 (also called STK24), MST4, and YSK1 (also called STK25 or SOK1)...
  48. Yang Z, Zheng B, Zhang Y, He M, Zhang X, Ma D, et al. miR-155-dependent regulation of mammalian sterile 20-like kinase 2 (MST2) coordinates inflammation, oxidative stress and proliferation in vascular smooth muscle cells. Biochim Biophys Acta. 2015;1852:1477-89 pubmed publisher
    ..Notably, expression of the miR-155-target protein mammalian sterile 20-like kinase 2 (MST2) was increased in the injured arteries of miR-155-/- mice...
  49. An S, Yang Y, Ward R, Liu Y, Guo X, Xu T. A-Raf: A new star of the family of raf kinases. Crit Rev Biochem Mol Biol. 2015;50:520-31 pubmed publisher
    ..These include the inhibition of apoptosis by binding to MST2, acting as safeguard against oncogenic transformation by suppressing extracellular signal-regulated kinases (ERK) ..
  50. Fan F, He Z, Kong L, Chen Q, Yuan Q, Zhang S, et al. Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration. Sci Transl Med. 2016;8:352ra108 pubmed publisher
    ..Kinases MST1 and MST2 (MST1/2), the mammalian Hippo orthologs, are central components of this pathway and are, therefore, strong target ..
  51. Sun T, Pepling M, Diaz F. Lats1 Deletion Causes Increased Germ Cell Apoptosis and Follicular Cysts in Mouse Ovaries. Biol Reprod. 2015;93:22 pubmed publisher
    ..Here, the expression of Hippo pathway components including Wwtr1, Stk4, Stk3, Lats2, and Yap1 transcripts were decreased by 50% in mouse ovaries between 2 and 8 days of age while expression ..
  52. Rauch J, VanDamme D, Mack B, McCann B, Volinsky N, Blanco A, et al. Differential localization of A-Raf regulates MST2-mediated apoptosis during epithelial differentiation. Cell Death Differ. 2016;23:1283-95 pubmed publisher
    ..We recently identified A-Raf as a potent inhibitor of the proapoptotic mammalian sterile 20-like kinase (MST2) tumor suppressor pathway in several cancer entities including head and neck, colon, and breast...
  53. 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. ..
  54. Romano D, Maccario H, Doherty C, Quinn N, Kolch W, Matallanas D. The differential effects of wild-type and mutated K-Ras on MST2 signaling are determined by K-Ras activation kinetics. Mol Cell Biol. 2013;33:1859-68 pubmed publisher
    ..and apoptosis through activation of extracellular signal-regulated kinase (ERK) and AKT pathways and the MST2 pathway, respectively. The biological outcome is determined by the balance and cross talk between these pathways...
  55. 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
    ..The expression of MST1 or MST2 was sufficient to stabilize p21 in a JNK- and Thr57-dependent manner, while the stabilization of p21 by actin ..
  56. Kanwal S, Jamil F, Ali A, Sehgal S. Comparative Modeling, Molecular Docking, and Revealing of Potential Binding Pockets of RASSF2; a Candidate Cancer Gene. Interdiscip Sci. 2017;9:214-223 pubmed publisher
    ..It stabilizes STK3/MST2 by protecting it from proteasomal degradation. RASSF2 plays a significant role against the inhibition of cancer...
  57. Shin S, Nguyen L. Unveiling Hidden Dynamics of Hippo Signalling: A Systems Analysis. Genes (Basel). 2016;7: pubmed publisher
    ..Akt displays opposing, dose-dependent functions towards ERK, which are mediated by the balance between the Raf-1/MST2 protein interaction module and the LATS1 mediated feedback regulation...
  58. Flury V, Georgescu P, Iesmantavicius V, Shimada Y, Kuzdere T, Braun S, et al. The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1. Mol Cell. 2017;67:294-307.e9 pubmed publisher
    ..We found that Pdp3 recruits the histone acetyltransferase Mst2 to H3K36me3-marked chromatin. Thereby, Mst2 binds to all transcriptionally active regions genome-wide...
  59. 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
    The serine/threonine protein kinases Mst1 and Mst2 can be activated by cellular stressors including hydrogen peroxide...
  60. 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 ..
  61. Schagdarsurengin U, Richter A, Hornung J, Lange C, Steinmann K, Dammann R. Frequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequences. Mol Cancer. 2010;9:264 pubmed publisher
    ..In our study, we analyzed the role of RASSF2, RASSF3, RASSF4, RASSF5A, RASSF5C and RASSF6 and the effectors MST1, MST2 and WW45 in thyroid carcinogenesis...
  62. Mardin B, Lange C, Baxter J, Hardy T, Scholz S, Fry A, et al. Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat Cell Biol. 2010;12:1166-76 pubmed publisher
    ..Here, we report that two Hippo pathway components, the mammalian sterile 20-like kinase 2 (Mst2) and the scaffold protein Salvador (hSav1), directly interact with Nek2A and regulate its ability to localize to ..
  63. Park B, Lee Y. Phosphorylation of SAV1 by mammalian ste20-like kinase promotes cell death. BMB Rep. 2011;44:584-9 pubmed
    ..We performed a mass spectrometric analysis of the SAV1 protein that was co-expressed with MST2. Phosphorylation was detected at Thr-26, Ser-27, Ser-36 and Ser-269...
  64. Meng F, Zhou R, Wu S, Zhang Q, Jin Q, Zhou Y, et al. Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation. Genes Dev. 2016;30:1086-100 pubmed publisher
    ..Through a functional screen of the human kinome, we found that mammalian sterile 20-like kinase 1 (Mst1), but not Mst2, profoundly inhibited cytosolic nucleic acid sensing...
  65. Li F, Bullough K, Vashisht A, Wohlschlegel J, Philpott C. Poly(rC)-Binding Protein 2 Regulates Hippo Signaling To Control Growth in Breast Epithelial Cells. Mol Cell Biol. 2016;36:2121-31 pubmed publisher
    ..Here, we show that PCBP2 forms a complex with the Hippo pathway components Salvador (Sav1), Mst1, Mst2, and Lats1 in human cells and mouse tissues...
  66. Lyu Z, Qin N, Tyasi T, Zhu H, Liu D, Yuan S, et al. The Hippo/MST Pathway Member SAV1 Plays a Suppressive Role in Development of the Prehierarchical Follicles in Hen Ovary. PLoS ONE. 2016;11:e0160896 pubmed publisher
    ..we found the intracellular SAV1 physically interacts with each of the pathway members, including STK4/MST1, STK3/MST2, LATS1 and MOB2 using western blotting...
  67. Couzens A, Xiong S, Knight J, Mao D, Guettler S, Picaud S, et al. MOB1 Mediated Phospho-recognition in the Core Mammalian Hippo Pathway. Mol Cell Proteomics. 2017;16:1098-1110 pubmed publisher
    ..The core of the pathway consists of a short kinase cascade: MST1 and MST2 phosphorylate and activate LATS1 and LATS2, which in turn phosphorylate and inactivate key transcriptional ..
  68. Xu S, Wu H, Nie H, Yue L, Jiang H, Xiao S, et al. AIF downregulation and its interaction with STK3 in renal cell carcinoma. PLoS ONE. 2014;9:e100824 pubmed publisher
    ..Further analysis revealed that AIF interacted with STK3, a known regulator of apoptosis, and enhanced its phosphorylation at Thr180...
  69. Yin H, Bogorad R, Barnes C, Walsh S, Zhuang I, Nonaka H, et al. RNAi-nanoparticulate manipulation of gene expression as a new functional genomics tool in the liver. J Hepatol. 2016;64:899-907 pubmed publisher
    ..targeting two kinases of the Hippo pathway, namely, mammalian Ste20 family kinases 1 and 2 (Mst1 and Mst2), and an upstream regulator, neurofibromatosis type II (Nf2)...
  70. Rybarczyk A, Klacz J, Wronska A, Matuszewski M, Kmiec Z, Wierzbicki P. Overexpression of the YAP1 oncogene in clear cell renal cell carcinoma is associated with poor outcome. Oncol Rep. 2017;38:427-439 pubmed publisher
    ..Hippo signaling, with its key kinases, MST2 and large tumor suppressor kinase 1 (LATS1), plays a significant role in the negative regulation of the amount ..
  71. Kang J, Wang J, Yao Z, Hu Y, Ma S, Fan Q, et al. Fascin induces melanoma tumorigenesis and stemness through regulating the Hippo pathway. Cell Commun Signal. 2018;16:37 pubmed publisher
    ..Co-IP and in vitro GST pulldown experiments were used to test the interaction between fascin and MST2. Fascin regulates tumorigenesis and cancer cell stemness in melanoma through inhibition of the Hippo pathway kinase ..
  72. Dong Q, Fu L, Zhao Y, Xie C, Li Q, Wang E. TNFAIP8 interacts with LATS1 and promotes aggressiveness through regulation of Hippo pathway in hepatocellular carcinoma. Oncotarget. 2017;8:15689-15703 pubmed publisher
    ..Collectively, the present study provides a novel finding that TNFAIP8 promotes HCC progression through LATS1-YAP signaling pathway. TNFAIP8 may serve as a candidate biomarker for poor prognosis and a target for new therapies. ..
  73. Riechers S, Butland S, Deng Y, Skotte N, Ehrnhoefer D, Russ J, et al. Interactome network analysis identifies multiple caspase-6 interactors involved in the pathogenesis of HD. Hum Mol Genet. 2016;25:1600-18 pubmed publisher
    ..One protein of interest, STK3, a pro-apoptotic kinase, was validated biochemically to be a CASP6 substrate...
  74. Deng Y, Pang A, Wang J. Regulation of mammalian STE20-like kinase 2 (MST2) by protein phosphorylation/dephosphorylation and proteolysis. J Biol Chem. 2003;278:11760-7 pubmed
    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...
  75. Seidel C, Schagdarsurengin U, Blümke K, Wurl P, Pfeifer G, Hauptmann S, et al. Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma. Mol Carcinog. 2007;46:865-71 pubmed
    ..RASSF1A is localized to microtubules and binds the apoptotic kinases MST1 and MST2. It has been shown that this interaction is mediated by the Sav-RASSF-Hpo domain, which is an interaction domain ..
  76. Kilili G, Kyriakis J. Mammalian Ste20-like kinase (Mst2) indirectly supports Raf-1/ERK pathway activity via maintenance of protein phosphatase-2A catalytic subunit levels and consequent suppression of inhibitory Raf-1 phosphorylation. J Biol Chem. 2010;285:15076-87 pubmed publisher
    ..Mammalian sterile 20-like kinase-2 (Mst2) is a mammalian Hpo orthologue, and numerous studies implicate Mst2 as a tumor suppressor...
  77. Guo C, Zhang X, Pfeifer G. The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2. J Biol Chem. 2011;286:6253-61 pubmed publisher
    The RASSF1A tumor suppressor protein interacts with the pro-apoptotic mammalian STE20-like kinases MST1 and MST2 and induces their autophosphorylation and activation, but the mechanism of how RASSF1A activates MST1/2 is unclear...
  78. Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, et al. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell. 2011;147:759-72 pubmed publisher
    ..This study links the CSC concept to the Hippo pathway in breast cancer and reveals a mechanistic basis of the control of Hippo kinases by cell polarity. ..
  79. Song J, Hong H, Choi S, Lee Y, Yamashita E, Bae S, et al. Crystallization and preliminary X-ray crystallographic study of the human MST2 SARAH domain. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011;67:1403-5 pubmed publisher
    The SARAH domain at the C-terminus of human MST2 (residues 436-484) was overproduced and purified using an Escherichia coli expression system. The purified domain was crystallized using the hanging-drop vapour-diffusion technique...
  80. 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
    ..We sought to understand the role of MST2 kinase and Salvador homolog 1 (SAV1), a scaffolding protein that functions in the MST pathway, in adipocyte ..
  81. Liu W, Wu J, Xiao L, Bai Y, Qu A, Zheng Z, et al. Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway. PLoS ONE. 2012;7:e36562 pubmed publisher
    ..stress-induced neuronal cell death through phosphorylating MST1 at Y433, which is not conserved among mammalian MST2, Drosophila Hippo and C.elegans cst-1/2...
  82. Song J, Hong H, Yamashita E, Park I, Lee S. Low pH-driven folding of WW45-SARAH domain leads to stabilization of the WW45-Mst2 complex. J Biochem. 2015;158:181-8 pubmed publisher
    ..of molecular properties found that the acidic-stable fold of WW45-SARAH enhances a heterotypic interaction with Mst2-SARAH...
  83. Chen X, Chen Y, Dong J. MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity. Cell Signal. 2016;28:1826-1832 pubmed publisher
    ..Here, we report a novel mechanism for phospho-regulation of MST2 in mitosis and its biological significance in cancer...
  84. Seo H, Choi Y, Kim M, Kang K, Urano T, Lee D. The 19S proteasome is directly involved in the regulation of heterochromatin spreading in fission yeast. J Biol Chem. 2017;292:17144-17155 pubmed publisher
    ..Further analysis revealed Mst2, another factor that antagonizes heterochromatin spreading, may function redundantly with Rpt4...
  85. Liu M, Liu S, Tan W, Tang F, Long J, Li Z, et al. Gaseous signalling molecule SO2 via Hippo?MST pathway to improve myocardial fibrosis of diabetic rats. Mol Med Rep. 2017;16:8953-8963 pubmed publisher
    ..The expression of ERS and Hippo?MST pathway?associated proteins, including CHOP, GRP94, MST1 and MST2, were significantly upregulated. By contrast, these above?mentioned changes were reversed by SO2 treatment...
  86. Bren A, Welch M, Blat Y, Eisenbach M. Signal termination in bacterial chemotaxis: CheZ mediates dephosphorylation of free rather than switch-bound CheY. Proc Natl Acad Sci U S A. 1996;93:10090-3 pubmed
    ..We suggest that CheZ affects switch-bound CheY approximately P by shifting the equilibrium between bound and free CheY approximately P. ..
  87. Wang H, Fecteau K. Detection of a novel quiescence-dependent protein kinase. J Biol Chem. 2000;275:25850-7 pubmed
    ..Using a specific antibody to Krs1/Mst2 protein, we found that p33(QIK) is related to p63(Krs1) and is distinguishable from a 36-kDa protein kinase, ..
  88. Fenton S, Dallol A, Agathanggelou A, Hesson L, Ahmed Choudhury J, Baksh S, et al. Identification of the E1A-regulated transcription factor p120 E4F as an interacting partner of the RASSF1A candidate tumor suppressor gene. Cancer Res. 2004;64:102-7 pubmed
    ..As p120(E4F) has been reported previously to interact with p14ARF, retinoblastoma, and p53, these findings provide an important link between the function of RASSF1A and other major human tumor suppressor genes. ..
  89. Liu L, Baier K, Dammann R, Pfeifer G. The tumor suppressor RASSF1A does not interact with Cdc20, an activator of the anaphase-promoting complex. Cell Cycle. 2007;6:1663-5 pubmed
    ..Here, we have used different methods to investigate the association of RASSF1A and Cdc20. We show that there is no interaction between RASSF1A and Cdc20 and conclude that further investigation of the mitotic role of RASSF1A is required. ..
  90. Hirabayashi S, Nakagawa K, Sumita K, Hidaka S, Kawai T, Ikeda M, et al. Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to form the scaffold to activate nuclear Dbf2-related kinase 1. Oncogene. 2008;27:4281-92 pubmed publisher
    ..Okadaic acid (OA), which activates MST2, facilitates the complex formation of MOB1, MST2 and NDR1 in HEK293FT cells...
  91. Hamilton G, Yee K, Scrace S, O Neill E. ATM regulates a RASSF1A-dependent DNA damage response. Curr Biol. 2009;19:2020-5 pubmed publisher
    ..Ras association domain-containing family 1A (RASSF1A) promotes apoptosis by signaling through the MST2 and LATS1 kinases, leading to stabilization of the YAP1/p73 transcriptional complex...
  92. 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