Lats1

Summary

Gene Symbol: Lats1
Description: large tumor suppressor
Alias: AW208599, serine/threonine-protein kinase LATS1, WARTS protein kinase, large tumor suppressor homolog 1, large tumor supressor, homolog 1, lats1
Species: mouse
Products:     Lats1

Top Publications

  1. Tao W, Zhang S, Turenchalk G, Stewart R, St John M, Chen W, et al. Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. Nat Genet. 1999;21:177-81 pubmed
    ..Here, we have isolated mammalian homologues of Drosophila lats. Human LATS1 suppresses tumour growth and rescues all developmental defects, including embryonic lethality in flies...
  2. St John M, Tao W, Fei X, Fukumoto R, Carcangiu M, Brownstein D, et al. Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat Genet. 1999;21:182-6 pubmed
    ..Mosaic flies carrying somatic cells that are mutant for lats develop large tumours in many organs. The human LATS1 homologue rescues embryonic lethality and inhibits tumour growth in lats mutant flies, demonstrating the ..
  3. Turenchalk G, St John M, Tao W, Xu T. The role of lats in cell cycle regulation and tumorigenesis. Biochim Biophys Acta. 1999;1424:M9-M16 pubmed
  4. 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
    ..Overexpression of YAP2 in HEK293 cells promoted apoptosis, whereas the Mst2/Lats1-induced phosphorylation of YAP partially rescued the cells from apoptotic death...
  5. 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...
  6. 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
    ..Thus, our study revealed a new connection between KIBRA and mammalian Hippo signaling. ..
  7. 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
    ..we show that DLG5 inhibits the association between MST1/2 and large tumor suppressor homologs 1/2 (LATS1/2), uses its scaffolding function to link MST1/2 with MARK3, and inhibits MST1/2 kinase activity...
  8. Pefani D, Latusek R, Pires I, Grawenda A, Yee K, Hamilton G, et al. RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2. Nat Cell Biol. 2014;16:962-71, 1-8 pubmed publisher
    ..Here we demonstrate that the Hippo pathway kinase LATS1 interacts with CDK2 in response to genotoxic stress to constrain pS3291-BRCA2 and support RAD51 nucleofilaments, ..
  9. 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
    ..Previous studies with overexpressed proteins have shown that YAP is phosphorylated by its upstream kinase, Lats1/2, on multiple sites, including an evolutionarily conserved 14-3-3-binding site whose phosphorylation is believed ..

More Information

Publications34

  1. 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...
  2. Szymaniak A, Mahoney J, Cardoso W, Varelas X. Crumbs3-Mediated Polarity Directs Airway Epithelial Cell Fate through the Hippo Pathway Effector Yap. Dev Cell. 2015;34:283-96 pubmed publisher
    ..We show that Crb3 promotes the interaction between Yap and the Hippo pathway kinases Lats1/2 at apical cell junctions to induce Yap phosphorylation and cytoplasmic retention, which drive cell ..
  3. 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
    ..that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth...
  4. Pisarska M, Kuo F, Bentsi Barnes I, Khan S, Barlow G. LATS1 phosphorylates forkhead L2 and regulates its transcriptional activity. Am J Physiol Endocrinol Metab. 2010;299:E101-9 pubmed publisher
    ..We found that FOXL2 is phosphorylated at a serine residue and, using yeast two-hybrid screening, identified LATS1 as a potential FOXL2-interacting protein...
  5. Siam R, Harada R, Cadieux C, Battat R, Vadnais C, Nepveu A. Transcriptional activation of the Lats1 tumor suppressor gene in tumors of CUX1 transgenic mice. Mol Cancer. 2009;8:60 pubmed publisher
    b>Lats1 (large tumor suppressor 1) codes for a serine/threonine kinase that plays a role in the progression through mitosis...
  6. 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
  7. 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. ..
  8. Xu T, Wang W, Zhang S, Stewart R, Yu W. Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development. 1995;121:1053-63 pubmed
    ..Mutations in lats cause dramatic overproliferation phenotypes and various developmental defects in both mosaic animals and homozygous mutants. ..
  9. 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
    The Hippo signaling pathway is essential for regulating proliferation and apoptosis in mammalian cells. The LATS1 kinase is a core member of the Hippo signaling pathway that phosphorylates and inactivates the transcriptional co-..
  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. 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
    ..Moreover, WW45 is required for MST1 activation and translocation to the nucleus for subsequent LATS1/2 activation upon differentiation signal...
  12. 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. ..
  13. Chiyoda T, Sugiyama N, Shimizu T, Naoe H, Kobayashi Y, Ishizawa J, et al. LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression. J Cell Biol. 2012;197:625-41 pubmed publisher
    ..In contrast, no phosphatase substrates of LATS1/WARTS kinase, the mammalian equivalent of Dbf2, has been reported...
  14. Jiang Z, Yu N, Kuang P, Chen M, Shao F, Martin G, et al. Trinucleotide repeat containing 6a (Tnrc6a)-mediated microRNA function is required for development of yolk sac endoderm. J Biol Chem. 2012;287:5979-87 pubmed publisher
    ..growth arrest and apoptosis phenotype are associated with significant derepression of Cdkn1a (p21), Cdkn1c (P27), Lats1, Lats2, Rb1, Rbl, Bim, and Pten, known targets of miRNAs from miR-17/20/93/106 clusters highly expressed in yolk ..
  15. 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. ..
  16. Visser Grieve S, Zhou Z, She Y, Huang H, Cyr T, Xu T, et al. LATS1 tumor suppressor is a novel actin-binding protein and negative regulator of actin polymerization. Cell Res. 2011;21:1513-6 pubmed publisher
  17. 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. ..
  18. 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...
  19. 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. ..
  20. Wennmann D, Vollenbröker B, Eckart A, Bonse J, Erdmann F, Wolters D, et al. The Hippo pathway is controlled by Angiotensin II signaling and its reactivation induces apoptosis in podocytes. Cell Death Dis. 2014;5:e1519 pubmed publisher
    ..Thus, our work indicates that the control of LATS activation and subsequent YAP localization is important for podocyte homeostasis and survival. ..
  21. 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. ..
  22. Moleirinho S, Patrick C, Tilston Lünel A, Higginson J, Angus L, Antkowiak M, et al. Willin, an upstream component of the hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts. PLoS ONE. 2013;8:e60028 pubmed publisher
    ..These results show that Willin modulates sciatic nerve fibroblast activity indicating that Willin may have a potential role in the regeneration of the peripheral nervous system. ..
  23. Gregorieff A, Liu Y, Inanlou M, Khomchuk Y, Wrana J. Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer. Nature. 2015;526:715-8 pubmed publisher
    ..Moreover, our findings reveal a key role for the Yap regenerative pathway in driving cancer initiation. ..
  24. 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. ..
  25. 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 ..