Gene Symbol: Mst1
Description: macrophage stimulating 1 (hepatocyte growth factor-like)
Alias: D3F15S2h, D9H3F15S2, DNF15S2h, Hgfl, hepatocyte growth factor-like protein, MSP, macrophage stimulatory protein
Species: mouse
Products:     Mst1

Top Publications

  1. Odashima M, Usui S, Takagi H, Hong C, Liu J, Yokota M, et al. Inhibition of endogenous Mst1 prevents apoptosis and cardiac dysfunction without affecting cardiac hypertrophy after myocardial infarction. Circ Res. 2007;100:1344-52 pubmed
    Mammalian sterile 20-like kinase-1 (Mst1) plays an important role in mediating cardiac myocyte apoptosis in response to ischemia/reperfusion...
  2. Morrison A, Wilson C, Ray M, Correll P. Macrophage-stimulating protein, the ligand for the stem cell-derived tyrosine kinase/RON receptor tyrosine kinase, inhibits IL-12 production by primary peritoneal macrophages stimulated with IFN-gamma and lipopolysaccharide. J Immunol. 2004;172:1825-32 pubmed
    ..We have shown previously that macrophage-stimulating protein (MSP), the ligand for the stem cell-derived tyrosine kinase/recepteur d'origine nantais (RON) receptor, inhibits NO ..
  3. Yoshimura T, Yuhki N, Wang M, Skeel A, Leonard E. Cloning, sequencing, and expression of human macrophage stimulating protein (MSP, MST1) confirms MSP as a member of the family of kringle proteins and locates the MSP gene on chromosome 3. J Biol Chem. 1993;268:15461-8 pubmed
    ..hepatoma (HepG2) cell line library was screened with an oligonucleotide probe for macrophage stimulating protein (MSP) to clone an MSP cDNA. Deduced sequences of isolated clones were compared with peptide fragment sequences of MSP...
  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
    ..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 ..
  5. Del Re D, Matsuda T, Zhai P, Maejima Y, Jain M, Liu T, et al. Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL. Mol Cell. 2014;54:639-50 pubmed publisher
    ..The core component of this cascade, Mst1 in mammalian cells, is sufficient to promote apoptosis...
  6. Katagiri K, Imamura M, Kinashi T. Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. Nat Immunol. 2006;7:919-28 pubmed
    ..Here we have identified the kinase Mst1 as a critical effector of RAPL. RAPL regulated the localization and kinase activity of Mst1...
  7. Dong Y, Du X, Ye J, Han M, Xu T, Zhuang Y, et al. A cell-intrinsic role for Mst1 in regulating thymocyte egress. J Immunol. 2009;183:3865-72 pubmed publisher
    The MST1 kinase was recently identified as playing an essential role in the promotion of lymphocyte polarization and adhesion stimulated by chemokines and TCR signaling...
  8. 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...
  9. Lee J, Shin J, Hwang S, Gwag B, McKee A, Lee J, et al. MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS. Proc Natl Acad Sci U S A. 2013;110:12066-71 pubmed publisher
    ..Here we show that genetic deficiency of mammalian sterile 20-like kinase 1 (MST1) delays disease onset and extends survival in mice expressing the ALS-associated G93A mutant of human SOD1...

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
    The Mst1 kinase is an important regulator of murine T cell adhesion, migration, proliferation, and apoptosis. In this study, we analyze mice lacking both Mst1 and Mst2 in hematopoietic cells...
  2. Gaudino G, Avantaggiato V, Follenzi A, Acampora D, Simeone A, Comoglio P. The proto-oncogene RON is involved in development of epithelial, bone and neuro-endocrine tissues. Oncogene. 1995;11:2627-37 pubmed
    ..showed that the proto-oncogene RON encodes the tyrosine kinase receptor for Macrophage Stimulating Protein (MSP), originally isolated as a chemotactic factor for peritoneal macrophages...
  3. Praskova M, Xia F, Avruch J. MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Curr Biol. 2008;18:311-21 pubmed publisher
    b>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...
  4. 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
    ..the role 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...
  5. Katagiri K, Katakai T, Ebisuno Y, Ueda Y, Okada T, Kinashi T. Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes. EMBO J. 2009;28:1319-31 pubmed publisher
    ..Here, we show that the Ste20-like kinase Mst1 plays crucial roles in lymphocyte trafficking in vivo...
  6. Zhou D, Medoff B, Chen L, Li L, Zhang X, Praskova M, et al. The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells. Proc Natl Acad Sci U S A. 2008;105:20321-6 pubmed publisher
    The Mst1 and Mst2 protein kinases are the mammalian homologs of hippo, a major inhibitor of cell proliferation in Drosophila. Mst1 is most abundant in lymphoid tissues...
  7. Ueda Y, Katagiri K, Tomiyama T, Yasuda K, Habiro K, Katakai T, et al. Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus. Nat Commun. 2012;3:1098 pubmed publisher
    Thymocyte trafficking has an important role in thymic selection. Here we show that the Hippo homologue Mst1 is required for thymocyte migration and antigen recognition by LFA-1 and ICAM-1 within the medulla...
  8. Chae J, Gil Hwang S, Lim D, Choi E. Thioredoxin-1 functions as a molecular switch regulating the oxidative stress-induced activation of MST1. Free Radic Biol Med. 2012;53:2335-43 pubmed publisher
    The mammalian STE20-like kinase-1 (MST1), a multifunctional serine-threonine kinase in mammalian cells, has been recently implicated in the mediation of oxidative stress-induced signaling processes that lead to cell death...
  9. Degen S, Gilbert D, Jenkins N, Copeland N. Assignment of the gene coding for hepatocyte growth factor-like protein to mouse chromosome 9. Genomics. 1992;13:1368-9 pubmed
    The gene coding for hepatocyte growth factor-like protein has been localized to mouse chromosome 9 at a locus (Hgfl) distal to the Trf locus. The likely gene order in this region is centromere-Trf-Gnai-2-Hgfl-Cck...
  10. Hess K, Waltz S, Chan E, Degen S. Receptor tyrosine kinase Ron is expressed in mouse reproductive tissues during embryo implantation and is important in trophoblast cell function. Biol Reprod. 2003;68:1267-75 pubmed
    Ron is a receptor tyrosine kinase that is activated by the binding of hepatocyte growth factor-like (HGFL) protein. Mutations in the catalytic domain of this receptor result in an aggressively invasive phenotype...
  11. Teal H, Craici A, Paulson R, Correll P. Macrophage-stimulating protein cooperates with erythropoietin to induce colony formation and MAP kinase activation in primary erythroid progenitor cells. J Hematother Stem Cell Res. 2003;12:165-77 pubmed
    ..In this report, we show that macrophage-stimulating protein (MSP), the ligand for full-length STK, can also cooperate with Epo to enhance burst-forming units-erythroid (BFU-E) ..
  12. Li J, Du X, Shi H, Deng K, Chi H, Tao W. Mammalian Sterile 20-like Kinase 1 (Mst1) Enhances the Stability of Forkhead Box P3 (Foxp3) and the Function of Regulatory T Cells by Modulating Foxp3 Acetylation. J Biol Chem. 2015;290:30762-70 pubmed publisher
    ..Here we report that Mst1 can enhance Foxp3 stability, its transcriptional activity, and Treg function by modulating the Foxp3 protein at the ..
  13. 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
    Here we show that Mst1, a proapoptotic kinase, impairs protein quality control mechanisms in the heart through inhibition of autophagy...
  14. Park E, Kim M, Song J, Roh K, Lee R, Kim T. MST1 deficiency promotes B cell responses by CD4+ T cell-derived IL-4, resulting in hypergammaglobulinemia. Biochem Biophys Res Commun. 2017;489:56-62 pubmed publisher
    b>MST1 deficiency causes T and B cell lymphopenia, resulting in combined immunodeficiency. However, MST1-deficient patients also exhibit autoimmune-like symptoms such as hypergammaglobulinemia and autoantibody production...
  15. Kim T, Lee D, Kim S, Shin S, Seo E, Lim D. Mammalian sterile 20-like kinase 1 suppresses lymphoma development by promoting faithful chromosome segregation. Cancer Res. 2012;72:5386-95 pubmed publisher
    ..Mammalian sterile 20-like kinase 1 (MST1), the core component of the Hippo signaling pathway, is highly expressed in hematopoietic cells...
  16. Muraoka R, Sun W, Colbert M, Waltz S, Witte D, Degen J, et al. The Ron/STK receptor tyrosine kinase is essential for peri-implantation development in the mouse. J Clin Invest. 1999;103:1277-85 pubmed
    ..kinase is a member of the c-Met family of receptors and is activated by hepatocyte growth factor-like protein (HGFL)...
  17. Kurz A, Pruenster M, Rohwedder I, Ramadass M, Schäfer K, Harrison U, et al. MST1-dependent vesicle trafficking regulates neutrophil transmigration through the vascular basement membrane. J Clin Invest. 2016;126:4125-4139 pubmed publisher
    ..Recent findings have associated mammalian sterile 20-like kinase 1 (MST1) loss of function with a human primary immunodeficiency disorder, suggesting that MST1 may be involved in immune ..
  18. Xiang C, Li J, Hu L, Huang J, Luo T, Zhong Z, et al. Hippo signaling pathway reveals a spatio-temporal correlation with the size of primordial follicle pool in mice. Cell Physiol Biochem. 2015;35:957-68 pubmed publisher
    ..pool, Western blot, Real-time PCR and immunohistochemistry were used, and the expression and localization of MST1, LATS2 and YAP1 mRNA and protein were examined in 3 d, 1 m, 5 m, 16 m postnatal mice ovary and the culture model of ..
  19. Xu X, Jaeger E, Wang X, Lagler Ferrez E, Batalov S, Mathis N, et al. Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. PLoS ONE. 2014;9:e105561 pubmed publisher
    ..b>Mst1 kinase is a key signal mediator required for both of these processes; however, its molecular mechanism remains ..
  20. Salojin K, Hamman B, Chang W, Jhaver K, Al Shami A, Crisostomo J, et al. Genetic deletion of Mst1 alters T cell function and protects against autoimmunity. PLoS ONE. 2014;9:e98151 pubmed publisher
    Mammalian sterile 20-like kinase 1 (Mst1) is a MAPK kinase kinase kinase which is involved in a wide range of cellular responses, including apoptosis, lymphocyte adhesion and trafficking...
  21. Yun H, Yoon J, Lee J, Noh K, Yoon K, Oh S, et al. Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling. EMBO J. 2011;30:2465-76 pubmed publisher
    ..Here, we show that Daxx and mammalian Ste20-like kinase-1 (MST1) mediate apoptosis elicited by interferon-? (IFN-?) in microglia...
  22. Li K, Christiano A, Copeland N, Gilbert D, Chu M, Jenkins N, et al. cDNA cloning and chromosomal mapping of the mouse type VII collagen gene (Col7a1): evidence for rapid evolutionary divergence of the gene. Genomics. 1993;16:733-9 pubmed
    ..This assignment confirms and extends the relationship between the mouse and the human chromosomes in this region of the genome. ..
  23. Ciccocioppo R, Economidou D, Cippitelli A, Cucculelli M, Ubaldi M, Soverchia L, et al. Genetically selected Marchigian Sardinian alcohol-preferring (msP) rats: an animal model to study the neurobiology of alcoholism. Addict Biol. 2006;11:339-55 pubmed summarizing almost 18 years of research in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats...
  24. Nishikimi A, Ishihara S, Ozawa M, Etoh K, Fukuda M, Kinashi T, et al. Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA-1 to the cell surface for lymphocyte trafficking. Sci Signal. 2014;7:ra72 pubmed publisher
    In lymphocytes, the kinase Mst1 is required for the proper organization of integrins in the plasma membrane at the leading edge of migrating cells, which is critical for lymphocyte trafficking...
  25. Chanda D, Li J, Oligschlaeger Y, Jeurissen M, Houben T, Walenbergh S, et al. MSP is a negative regulator of inflammation and lipogenesis in ex vivo models of non-alcoholic steatohepatitis. Exp Mol Med. 2016;48:e258 pubmed publisher
    ..Macrophage-stimulating protein (MSP) is a hepatokine that potentially has a beneficial role in hepatic lipid and glucose metabolism via the activation ..
  26. Gurusamy D, Ruiz Torres S, Johnson A, Smith D, Waltz S. Hepatocyte growth factor-like protein is a positive regulator of early mammary gland ductal morphogenesis. Mech Dev. 2014;133:11-22 pubmed publisher
    ..Hepatocyte growth factor-like protein [HGFL] is the only known ligand for the Ron receptor and recent studies have identified major roles for HGFL during ..
  27. Persons D, Paulson R, Loyd M, Herley M, Bodner S, Bernstein A, et al. Fv2 encodes a truncated form of the Stk receptor tyrosine kinase. Nat Genet. 1999;23:159-65 pubmed
    ..We conclude that the Fv2 locus encodes Ron, and that a naturally expressed, truncated form of Stk confers susceptibility to Friend virus-induced erythroleukaemia...
  28. Shott R, Majer A, Frost K, Booth S, Schang L. Activation of pro-survival CaMK4β/CREB and pro-death MST1 signaling at early and late times during a mouse model of prion disease. Virol J. 2014;11:160 pubmed publisher
    ..Hierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated...
  29. 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
    ..The activity of the core kinases MST1 and LATS1 increased during the early hypertrophic phase and returned to steady state levels in the proliferative ..
  30. Hu J, Zhang L, Yang Y, Guo Y, Fan Y, Zhang M, et al. Melatonin alleviates postinfarction cardiac remodeling and dysfunction by inhibiting Mst1. J Pineal Res. 2017;62: pubmed publisher
    ..Furthermore, melatonin significantly inhibited Mst1 phosphorylation while promoting Sirt1 expression after MI, which indicates that Mst1/Sirt1 signaling may serve as ..
  31. Wang T, Zhang L, Hu J, Duan Y, Zhang M, Lin J, et al. Mst1 participates in the atherosclerosis progression through macrophage autophagy inhibition and macrophage apoptosis enhancement. J Mol Cell Cardiol. 2016;98:108-16 pubmed publisher
    ..Here ApoE(-/-) mice were crossed with Mst1 knockout or Mst1 Tg mice to generate ApoE(-/-):Mst1(-/-) and ApoE(-/-):Mst1Tg mice...
  32. Yeung R, Hino O, Vilensky M, Buetow K, Szpirer C, Szpirer J, et al. Assignment of 22 loci in the rat by somatic hybrid and linkage analysis. Mamm Genome. 1993;4:585-8 pubmed
    ..Results of this study further support the extensive conservation of synteny between the rat and mouse and, to a lesser degree, between rat and human. ..
  33. You B, Huang S, Qin Q, Yi B, Yuan Y, Xu Z, et al. Glyceraldehyde-3-phosphate dehydrogenase interacts with proapoptotic kinase mst1 to promote cardiomyocyte apoptosis. PLoS ONE. 2013;8:e58697 pubmed publisher
    Mammalian sterile 20-like kinase 1 (Mst1) is a critical component of the Hippo signaling pathway, which regulates a variety of biological processes ranging from cell contact inhibition, organ size control, apoptosis and tumor suppression ..
  34. Xu X, Wang X, Todd E, Jaeger E, Vella J, Mooren O, et al. Mst1 Kinase Regulates the Actin-Bundling Protein L-Plastin To Promote T Cell Migration. J Immunol. 2016;197:1683-91 pubmed publisher
    ..The mammalian Ste20-like kinase 1 (Mst1) has been identified as a critical signaling mediator of T cell migration, and loss of Mst1 results in ..
  35. Zhang M, Zhang L, Hu J, Lin J, Wang T, Duan Y, et al. MST1 coordinately regulates autophagy and apoptosis in diabetic cardiomyopathy in mice. Diabetologia. 2016;59:2435-2447 pubmed publisher
    ..Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental ..
  36. Forgie A, Wyatt S, Correll P, Davies A. Macrophage stimulating protein is a target-derived neurotrophic factor for developing sensory and sympathetic neurons. Development. 2003;130:995-1002 pubmed
    Macrophage stimulating protein (MSP) is a pleiotropic growth factor that signals via the Ron receptor tyrosine kinase...
  37. Degen S, Stuart L, Han S, Jamison C. Characterization of the mouse cDNA and gene coding for a hepatocyte growth factor-like protein: expression during development. Biochemistry. 1991;30:9781-91 pubmed
    ..It is apparent that the majority of mRNA coding for HGF-like protein is expressed in liver. Messenger RNA is also expressed at a lower level in lung, adrenal, and placenta. ..
  38. Ray M, Yu S, Sharda D, Wilson C, Liu Q, Kaushal N, et al. Inhibition of TLR4-induced I?B kinase activity by the RON receptor tyrosine kinase and its ligand, macrophage-stimulating protein. J Immunol. 2010;185:7309-16 pubmed publisher
    ..In primary macrophages, the ligand for Ron, macrophage-stimulating protein (MSP), inhibits the expression of inducible NO synthase, a marker of classically activated macrophages, whereas ..
  39. Bezerra J, Witte D, Aronow B, Degen S. Hepatocyte-specific expression of the mouse hepatocyte growth factor-like protein. Hepatology. 1993;18:394-9 pubmed
    ..We conclude that although structurally similar to hepatocyte growth factor, hepatocyte growth factor-like protein is a novel protein synthesized primarily in hepatocytes. ..
  40. Geng C, Zhang Y, Gao Y, Tao W, Zhang H, Liu X, et al. Mst1 regulates hepatic lipid metabolism by inhibiting Sirt1 ubiquitination in mice. Biochem Biophys Res Commun. 2016;471:444-9 pubmed publisher
    Previous study showed mammalian Ste20-like kinase (Mst1) may serve as target for the development of new therapies for diabetes. However, the function of Mst1 involved in liver lipid metabolism has remained elusive...
  41. Sciarretta S, Zhai P, Maejima Y, Del Re D, Nagarajan N, Yee D, et al. mTORC2 regulates cardiac response to stress by inhibiting MST1. Cell Rep. 2015;11:125-36 pubmed publisher
    ..Here, we demonstrate that mTORC2 is a direct negative regulator of the MST1 kinase, a key component of the Hippo pathway...
  42. 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
    ..b>Mst1 and Mst2 are central components of this pathway that are essential for embryonic development, though their role in ..
  43. Wang S, Fan Y, Feng X, Sun C, Shi Z, Li T, et al. Nicorandil alleviates myocardial injury and post-infarction cardiac remodeling by inhibiting Mst1. Biochem Biophys Res Commun. 2018;495:292-299 pubmed publisher
    ..Interestingly, nicorandil increased Mst1 and p-Mst1 levels in cardiomyocytes subjected to MI injury...
  44. Roh K, Choi E. TRAF2 functions as an activator switch in the reactive oxygen species-induced stimulation of MST1. Free Radic Biol Med. 2016;91:105-13 pubmed publisher
    ..In particular, excessive ROS causes oxidative stress that leads to cell death. The mammalian STE20-like kinase-1 (MST1), a multifunctional serine-threonine kinase, plays a pivotal role in oxidative stress-induced cellular signaling ..
  45. Kauder S, Santell L, Mai E, Wright L, Luis E, N Diaye E, et al. Functional consequences of the macrophage stimulating protein 689C inflammatory bowel disease risk allele. PLoS ONE. 2013;8:e83958 pubmed publisher
    Macrophage stimulating protein (MSP) is a serum growth factor that binds to and activates the receptor tyrosine kinase, Recepteur d'Origine Nantais (RON)...
  46. Edgar A, Trost M, Watts C, Zaru R. A combination of SILAC and nucleotide acyl phosphate labelling reveals unexpected targets of the Rsk inhibitor BI-D1870. Biosci Rep. 2014;34: pubmed
    ..We confirmed that these kinases, including Slk, Lok and Mst1, are inhibited by BI-D1870 but to a much lesser extent by BIX 02565 and that phosphorylation of some of their ..
  47. Bezerra J, Carrick T, Degen J, Witte D, Degen S. Biological effects of targeted inactivation of hepatocyte growth factor-like protein in mice. J Clin Invest. 1998;101:1175-83 pubmed
    Hepatocyte growth factor-like protein (HGFL) is a liver-derived serum glycoprotein involved in cell proliferation and differentiation, and is proposed to have a fundamental role in embryogenesis, fertility, hematopoiesis, macrophage ..
  48. Lo H, Jin R, Sibbel G, Liu D, Karki A, Joens M, et al. A single transcription factor is sufficient to induce and maintain secretory cell architecture. Genes Dev. 2017;31:154-171 pubmed publisher
  49. Zhang M, Lin J, Wang S, Cheng Z, Hu J, Wang T, et al. Melatonin protects against diabetic cardiomyopathy through Mst1/Sirt3 signaling. J Pineal Res. 2017;63: pubmed publisher
    ..Furthermore, melatonin inhibited Mst1 phosphorylation and promoted Sirt3 expression in DCM...