Abstract
The Hippo tumor suppressor pathway is fundamental to the coordination of death, growth, proliferation, and differentiation on the cellular level. At the molecular level, a highly conserved Hippo core cassette is central for the regulation of effector activities such as the co-transcriptional activity of YAP. In particular, the mammalian MST1/2 serine/threonine protein kinases (termed Hippo kinase in Drosophila melanogaster) can act as central signal transducers as part of the Hippo core cassette. In this chapter we describe in vitro kinase assays using recombinant MST1/2 kinases and recombinant MST1/2 kinase substrate.
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References
Johnson R, Halder G (2014) The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov 13(1):63–79. https://doi.org/10.1038/nrd4161
Yu FX, Zhao B, Guan KL (2015) Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell 163(4):811–828. https://doi.org/10.1016/j.cell.2015.10.044
Meng Z, Moroishi T, Guan KL (2016) Mechanisms of Hippo pathway regulation. Genes Dev 30(1):1–17. https://doi.org/10.1101/gad.274027.115
Irvine KD, Harvey KF (2015) Control of organ growth by patterning and hippo signaling in Drosophila. Cold Spring Harb Perspect Biol 7(6):a019224
Sun S, Irvine KD (2016) Cellular organization and cytoskeletal regulation of the Hippo signaling network. Trends Cell Biol 26(9):694–704
Pan D (2010) The hippo signaling pathway in development and cancer. Dev Cell 19(4):491–505
Harvey KF, Zhang X, Thomas DM (2013) The Hippo pathway and human cancer. Nat Rev Cancer 13(4):246–257. https://doi.org/10.1038/nrc3458
Hoa L, Kulaberoglu Y, Gundogdu R, Cook D, Mavis M, Gomez M, Gomez V, Hergovich A (2016) The characterisation of LATS2 kinase regulation in Hippo-YAP signalling. Cell Signal 28(5):488–497. https://doi.org/10.1016/j.cellsig.2016.02.012
Praskova M, Xia F, Avruch J (2008) MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Curr Biol 18(5):311–321. https://doi.org/10.1016/j.cub.2008.02.006
Ni L, Zheng Y, Hara M, Pan D, Luo X (2015) Structural basis for Mob1-dependent activation of the core Mst-Lats kinase cascade in Hippo signaling. Genes Dev 29(13):1416–1431. https://doi.org/10.1101/gad.264929.115
Kim SY, Tachioka Y, Mori T, Hakoshima T (2016) Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway. Sci Rep 6:28488. https://doi.org/10.1038/srep28488
Couzens AL, Xiong S, Knight JD, Mao DY, Guettler S, Picaud S, Kurinov I, Filippakopoulos P, Sicheri F, Gingras A-C (2017) MOB1 mediated phospho-recognition in the core mammalian Hippo pathway. Mol Cell Proteomics 16(6):1098–1110
Xiong S, Couzens AL, Kean MJ, Mao DY, Guettler S, Kurinov I, Gingras A-C, Sicheri F (2017) Regulation of protein interactions by Mps One Binder (MOB1) phosphorylation. Mol Cell Proteomics 16(6):1111–1125
Kulaberoglu Y, Lin K, Holder M, Gai Z, Gomez M, Assefa Shifa B, Mavis M, Hoa L, Sharif AAD, Lujan C, Smith ESJ, Bjedov I, Tapon N, Wu G, Hergovich A (2017) Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control. Nat Commun 8(1):695. https://doi.org/10.1038/s41467-017-00795-y
Vrabioiu AM, Struhl G (2015) Fat/Dachsous signaling promotes Drosophila wing growth by regulating the conformational state of the NDR kinase Warts. Dev Cell 35(6):737–749
Zanconato F, Cordenonsi M, Piccolo S (2016) YAP/TAZ at the roots of cancer. Cancer Cell 29(6):783–803
Hergovich A (2016) The roles of ndr protein kinases in hippo signalling. Genes 7(5):21
Zhang L, Tang F, Terracciano L, Hynx D, Kohler R, Bichet S, Hess D, Cron P, Hemmings BA, Hergovich A (2015) NDR functions as a physiological YAP1 kinase in the intestinal epithelium. Curr Biol 25(3):296–305
Hergovich A (2011) MOB control: reviewing a conserved family of kinase regulators. Cell Signal 23(9):1433–1440. https://doi.org/10.1016/j.cellsig.2011.04.007
Sharif AA, Hergovich A (2017) The NDR/LATS protein kinases in immunology and cancer biology. In: Seminars in cancer biology. Elsevier.
Galan JA, Avruch J (2016) MST1/MST2 protein kinases: regulation and physiologic roles. Biochemistry 55(39):5507–5519
Qin F, Tian J, Zhou D, Chen L (2013) Mst1 and Mst2 kinases: regulations and diseases. Cell Biosci 3(1):31
Acknowledgments
The Hergovich laboratory was supported by the Wellcome Trust (090090/Z/09/Z), BBSRC (BB/I021248/1), Worldwide Cancer Research (AICR; 11-0634), UCL Cancer Research UK Centre and the National Institute for Health Research University College London Hospitals Biomedical Research Centre.
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Gomez, M., Kulaberoglu, Y., Hergovich, A. (2019). MST1/2 Kinase Assays Using Recombinant Proteins. In: Hergovich, A. (eds) The Hippo Pathway. Methods in Molecular Biology, vol 1893. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8910-2_24
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DOI: https://doi.org/10.1007/978-1-4939-8910-2_24
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