Lats2

Summary

Gene Symbol: Lats2
Description: large tumor suppressor 2
Alias: 4932411G09Rik, AV277261, AW228608, serine/threonine-protein kinase LATS2, kinase phosphorylated during mitosis protein, large tumor suppressor homolog 2, lats2, serine/threonine-protein kinase kpm
Species: mouse
Products:     Lats2

Top Publications

  1. McPherson J, Tamblyn L, Elia A, Migon E, Shehabeldin A, Matysiak Zablocki E, et al. Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. EMBO J. 2004;23:3677-88 pubmed
    The Drosophila melanogaster warts/lats tumour suppressor has two mammalian counterparts LATS1/Warts-1 and LATS2/Kpm. Here, we show that mammalian Lats orthologues exhibit distinct expression profiles according to germ cell layer origin...
  2. Kim M, Kim M, Lee S, Kuninaka S, Saya H, Lee H, et al. cAMP/PKA signalling reinforces the LATS-YAP pathway to fully suppress YAP in response to actin cytoskeletal changes. EMBO J. 2013;32:1543-55 pubmed publisher
    ..We also implicate neurofibromin 2 as an AKAP (A-kinase-anchoring protein) scaffold protein that facilitates the function of the cAMP/PKA-LATS-YAP pathway. Our study thus incorporates PKA as novel component of the Hippo pathway. ..
  3. Varelas X, Samavarchi Tehrani P, Narimatsu M, Weiss A, Cockburn K, Larsen B, et al. The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-?-SMAD pathway. Dev Cell. 2010;19:831-44 pubmed publisher
    ..Accordingly, disruption of the Crumbs complex enhances TGF-? signaling and predisposes cells to TGF-?-mediated epithelial-to-mesenchymal transitions. ..
  4. Yabuta N, Okada N, Ito A, Hosomi T, Nishihara S, Sasayama Y, et al. Lats2 is an essential mitotic regulator required for the coordination of cell division. J Biol Chem. 2007;282:19259-71 pubmed
    Tumor suppressor Lats2 is a member of the conserved Dbf2 kinase family. It localizes to the centrosome and has been implicated in regulation of the cell cycle and apoptosis. However, the in vivo function of this kinase remains unclear...
  5. Matsui Y, Nakano N, Shao D, Gao S, Luo W, Hong C, et al. Lats2 is a negative regulator of myocyte size in the heart. Circ Res. 2008;103:1309-18 pubmed publisher
    ..which in turn stimulates cell death and inhibits cell proliferation, mammalian homologs of Warts, termed Lats1 and Lats2, may mediate the function of Mst1...
  6. Zhang N, Bai H, David K, Dong J, Zheng Y, Cai J, et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell. 2010;19:27-38 pubmed publisher
    ..Our studies link Merlin/NF2 to mammalian Hippo signaling and implicate YAP activation as a mediator of pathologies relevant to Neurofibromatosis 2...
  7. 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. ..
  8. 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 mice ..
  9. Torigata K, Daisuke O, Mukai S, Hatanaka A, Ohka F, Motooka D, et al. LATS2 Positively Regulates Polycomb Repressive Complex 2. PLoS ONE. 2016;11:e0158562 pubmed publisher
    b>LATS2, a pivotal Ser/Thr kinase of the Hippo pathway, plays important roles in many biological processes. LATS2 also function in Hippo-independent pathway, including mitosis, DNA damage response and epithelial to mesenchymal transition...

More Information

Publications34

  1. 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
    ..These data reveal a direct connection between cell polarity proteins and Hippo, which is essential for proper development of multicellular organisms. ..
  2. Fujii K, Shi Z, Zhulyn O, Denans N, Barna M. Pervasive translational regulation of the cell signalling circuitry underlies mammalian development. Nat Commun. 2017;8:14443 pubmed publisher
    ..Altogether, this work reveals a new layer of translational control to major signalling components and gene regulatory networks that diversifies gene expression spatially across developing tissues. ..
  3. 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. ..
  4. Nishioka N, Inoue K, Adachi K, Kiyonari H, Ota M, Ralston A, et al. The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev Cell. 2009;16:398-410 pubmed publisher
    ..Thus, differential signaling between inside and outside cell populations leads to changes in cell fate specification during TE formation. ..
  5. 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. ..
  6. Tian Y, Liu Y, Wang T, Zhou N, Kong J, Chen L, et al. A microRNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice. Sci Transl Med. 2015;7:279ra38 pubmed publisher
    ..Our data demonstrate the ability of microRNA-based therapeutic approaches to promote mammalian cardiac repair and regeneration through the transient activation of cardiomyocyte proliferation. ..
  7. Szymaniak A, Mi R, McCarthy S, Gower A, Reynolds T, Mingueneau M, et al. The Hippo pathway effector YAP is an essential regulator of ductal progenitor patterning in the mouse submandibular gland. elife. 2017;6: pubmed publisher
    ..We further show that epithelial deletion of the Lats1 and Lats2 genes, which encode kinases that restrict nuclear Yap localization, results in morphogenesis defects ..
  8. Li C, Hu J, Lu H, Lan J, Du W, Galicia N, et al. ?E-catenin inhibits YAP/TAZ activity to regulate signalling centre formation during tooth development. Nat Commun. 2016;7:12133 pubmed publisher
    ..These findings point to a developmental mechanism by which ?E-catenin restricts YAP/TAZ activity to establish a group of non-dividing and specialized cells that constitute a signalling centre. ..
  9. Aylon Y, Sarver A, Tovy A, Ainbinder E, Oren M. Lats2 is critical for the pluripotency and proper differentiation of stem cells. Cell Death Differ. 2014;21:624-33 pubmed publisher
    ..We analyzed the involvement of the tumor-suppressor Lats2 in mouse embryonic stem cell (mESC) pluripotency and differentiation, and report that mESCs lacking Lats2 are ..
  10. Moon K, Kim H, Lee D, Rao M, Levine E, Lim D, et al. Differential Expression of NF2 in Neuroepithelial Compartments Is Necessary for Mammalian Eye Development. Dev Cell. 2018;44:13-28.e3 pubmed publisher
    ..Together, our findings reveal that Nf2 is a key player that orchestrates the differential growth of optic neuroepithelial compartments during vertebrate eye development. ..
  11. Yabuta N, Fujii T, Copeland N, Gilbert D, Jenkins N, Nishiguchi H, et al. Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts. Genomics. 2000;63:263-70 pubmed
    We have cloned and characterized LATS2, a novel mammalian homologue of the Drosophila tumor suppressor gene lats/warts...
  12. Ichikawa H, Shimizu K, Katsu R, Ohki M. Dual transforming activities of the FUS (TLS)-ERG leukemia fusion protein conferred by two N-terminal domains of FUS (TLS). Mol Cell Biol. 1999;19:7639-50 pubmed
    ..These results suggest that FUS-ERG may activate two independent oncogenic pathways during the leukemogenic process by modulating the expression of two different groups of genes simultaneously. ..
  13. Enger T, Samad Zadeh A, Bouchie M, Skarstein K, Galtung H, Mera T, et al. The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's syndrome. Lab Invest. 2013;93:1203-18 pubmed publisher
    ..Inhibition of Lats2, an upstream kinase that promotes TAZ phosphorylation, results in dysmorphogenesis of the SMG and impaired duct ..
  14. 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. ..
  15. Chen Q, Zhang N, Xie R, Wang W, Cai J, Choi K, et al. Homeostatic control of Hippo signaling activity revealed by an endogenous activating mutation in YAP. Genes Dev. 2015;29:1285-97 pubmed publisher
    ..These findings reveal a robust homeostatic mechanism that maintains physiological levels of YAP activity and caution against the assumptive use of YAP localization alone as a surrogate of YAP activity. ..
  16. Xiao L, Chen Y, Ji M, Dong J. KIBRA regulates Hippo signaling activity via interactions with large tumor suppressor kinases. J Biol Chem. 2011;286:7788-96 pubmed publisher
    ..Conversely, depletion of KIBRA by RNA interference reduces YAP phosphorylation. Furthermore, KIBRA stabilizes Lats2 by inhibiting its ubiquitination...
  17. Kim J, Kim Y, Kim J, Park D, Bae H, Lee D, et al. YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation. J Clin Invest. 2017;127:3441-3461 pubmed publisher
  18. Aylon Y, Gershoni A, Rotkopf R, Biton I, Porat Z, Koh A, et al. The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation. Genes Dev. 2016;30:786-97 pubmed publisher
    ..The LATS2 tumor suppressor is a core member of the Hippo pathway...
  19. An Y, Kang Q, Zhao Y, Hu X, Li N. Lats2 modulates adipocyte proliferation and differentiation via hippo signaling. PLoS ONE. 2013;8:e72042 pubmed publisher
    First identified in Drosophila and highly conserved in mammals, the Hippo pathway controls organ size. Lats2 is one of the core kinases of the Hippo pathway and plays major roles in cell proliferation by interacting with the downstream ..
  20. Moroishi T, Hayashi T, Pan W, Fujita Y, Holt M, Qin J, et al. The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity. Cell. 2016;167:1525-1539.e17 pubmed publisher
    ..Our observations uncover a key role of the Hippo pathway in modulating tumor immunogenicity and demonstrate a proof of concept for targeting LATS1/2 in cancer immunotherapy. ..
  21. Lorthongpanich C, Messerschmidt D, Chan S, Hong W, Knowles B, Solter D. Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation. Genes Dev. 2013;27:1441-6 pubmed publisher
    ..We therefore conclude that precisely timed YAP localization in early morulae is essential to prevent trophectoderm marker expression in, and lineage specification of, the ICM. ..
  22. Liang Y, Li Y, Li Z, Liu Z, Zhang Z, Chang S, et al. Mechanism of folate deficiency-induced apoptosis in mouse embryonic stem cells: Cell cycle arrest/apoptosis in G1/G0 mediated by microRNA-302a and tumor suppressor gene Lats2. Int J Biochem Cell Biol. 2012;44:1750-60 pubmed publisher
    ..role in mediating the effects of folate on cell proliferation and cell cycle-specific apoptosis by targeting Lats2 gene...
  23. Shao D, Zhai P, Del Re D, Sciarretta S, Yabuta N, Nojima H, et al. A functional interaction between Hippo-YAP signalling and FoxO1 mediates the oxidative stress response. Nat Commun. 2014;5:3315 pubmed publisher
    ..These results suggest that YAP is a nuclear co-factor of FoxO1 and that the Hippo pathway negatively affects cardiomyocyte survival by inhibiting the function of YAP-FoxO1. ..
  24. Singh A, Ramesh S, Cibi D, Yun L, Li J, Li L, et al. Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development. Cell Rep. 2016;15:1384-1393 pubmed publisher
    ..Our findings show a role for Hippo signaling in epicardial cell proliferation, EMT, and cell fate specification during cardiac organogenesis. ..
  25. Yabuta N, Mukai S, Okamoto A, Okuzaki D, Suzuki H, Torigata K, et al. N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability. J Cell Sci. 2013;126:508-20 pubmed publisher
    The tumor suppressors Lats1 and Lats2 are mediators of the Hippo pathway that regulates tissue growth and proliferation...