Cell Biosci. 2013 Aug 28;3(1):32. doi: 10.1186/2045-3701-3-32.
Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling.
Cell & bioscience
Alexander Hergovich
Affiliations
Affiliations
- Tumour Suppressor Signalling Networks laboratory, UCL Cancer Institute, University College London, London WC1E 6BT, UK. [email protected].
PMID: 23985307
PMCID: PMC3849777 DOI: 10.1186/2045-3701-3-32
Abstract
The metazoan Hippo pathway is an essential tumour suppressor signalling cascade that ensures normal tissue growth by co-ordinating cell proliferation, cell death and cell differentiation. Over the past years, various genetic and biochemical studies in Drosophila and mammals have defined a conserved core Hippo signalling module, composed of members of the Ste20-like kinase, the MOB co-activator and the AGC kinase families. In Drosophila, stimulated Hippo kinase phosphorylates and thereby activates the Mats/Warts complex, which consequently phosphorylates and inactivates the transcriptional co-activator Yorkie. In mammals, the counterparts of the Hippo/Mats/Warts/Yorkie cascade, namely MST1/2, MOB1A/B, LATS1/2 and YAP/TAZ, function in a similar fashion. These canonical Hippo pathways are so highly conserved that human MST2, hMOB1A and LATS1 can compensate for the loss of Hippo, Mats and Warts in flies. However, recent reports have shown that Hippo signalling is more diverse and complex, in particular in mammals. In this review, we summarize our current understanding of mammalian LATS1/2 kinases together with their closest relatives, the NDR1/2 kinases. The regulation of the LATS/NDR family of kinases will be discussed, followed by a summary of all currently known LATS/NDR substrates. Last, but not least, the biological roles of LATS/NDR kinases will be reviewed with specific emphasis on recent discoveries of canonical and non-canonical LATS/NDR functions in the extended Hippo pathway.
References
- Cancer Res. 2005 Aug 1;65(15):6568-75 - PubMed
- EMBO J. 2013 Mar 20;32(6):874-85 - PubMed
- Cancer Res. 2011 Mar 1;71(5):2010-20 - PubMed
- Nat Cell Biol. 2003 Oct;5(10):914-20 - PubMed
- Hum Mol Genet. 2012 Dec 15;21(26):5528-38 - PubMed
- Genomics. 2010 Dec;96(6):362-8 - PubMed
- J Biol Chem. 2004 May 28;279(22):23806-12 - PubMed
- Oncogene. 2013 Nov 7;32(45):5283-91 - PubMed
- Nat Cell Biol. 2003 Oct;5(10):921-7 - PubMed
- Mol Biol Cell. 2005 Feb;16(2):689-700 - PubMed
- Oncogene. 2005 Mar 17;24(12):2076-86 - PubMed
- J Biol Chem. 2007 Jun 29;282(26):19259-71 - PubMed
- J Biol Chem. 2012 Oct 5;287(41):34069-77 - PubMed
- Nat Genet. 1999 Feb;21(2):177-81 - PubMed
- EMBO J. 2004 Sep 15;23(18):3677-88 - PubMed
- Cell. 2006 Mar 24;124(6):1169-81 - PubMed
- Genes Dev. 1995 Mar 1;9(5):534-46 - PubMed
- FEBS Lett. 2002 Oct 9;529(2-3):319-24 - PubMed
- Dev Cell. 2010 Oct 19;19(4):491-505 - PubMed
- Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):E1312-20 - PubMed
- Cancer Res. 2011 Mar 15;71(6):2162-71 - PubMed
- Cell Cycle. 2010 Oct 1;9(19):3892-903 - PubMed
- Cell. 2012 Aug 17;150(4):780-91 - PubMed
- Mol Cell Biol. 2010 Sep;30(18):4507-20 - PubMed
- Breast Cancer Res. 2012 Dec 05;14(6):326 - PubMed
- Curr Opin Cell Biol. 2013 Apr;25(2):247-53 - PubMed
- Sci Signal. 2010 Jun 15;3(126):ra47 - PubMed
- Nat Genet. 1999 Feb;21(2):182-6 - PubMed
- Mol Cell. 2007 Feb 23;25(4):625-34 - PubMed
- J Cell Sci. 2011 Jan 1;124(Pt 1):57-67 - PubMed
- Nat Rev Mol Cell Biol. 2010 Jan;11(1):9-22 - PubMed
- EMBO J. 2012 Jan 4;31(1):29-43 - PubMed
- J Biochem. 2012 Oct;152(4):347-53 - PubMed
- Sci Signal. 2013 Jan 22;6(259):pe4 - PubMed
- Dev Cell. 2011 Nov 15;21(5):888-95 - PubMed
- Development. 1995 Apr;121(4):1053-63 - PubMed
- Nat Rev Mol Cell Biol. 2006 Apr;7(4):253-64 - PubMed
- Curr Biol. 2012 Sep 11;22(17):1587-94 - PubMed
- Dev Cell. 2009 Mar;16(3):398-410 - PubMed
- Genes Dev. 2006 Oct 1;20(19):2687-700 - PubMed
- Mol Cell Biol. 2005 Dec;25(24):11019-29 - PubMed
- Genes Dev. 2013 Feb 15;27(4):355-71 - PubMed
- Semin Cell Dev Biol. 2012 Sep;23(7):770-84 - PubMed
- Curr Biol. 2013 Feb 18;23(4):333-8 - PubMed
- Cell. 2011 Nov 11;147(4):759-72 - PubMed
- J Biol Chem. 2011 Feb 11;286(6):4364-70 - PubMed
- Dev Biol. 2010 May 15;341(2):360-74 - PubMed
- J Biol Chem. 2004 Aug 20;279(34):35228-35 - PubMed
- Nat Cell Biol. 2008 Jul;10(7):837-48 - PubMed
- J Clin Invest. 2012 Dec;122(12):4505-18 - PubMed
- Genetics. 2000 Dec;156(4):1817-28 - PubMed
- J Cell Biol. 2013 Jun 10;201(6):875-85 - PubMed
- Genes Dev. 2010 Jun 1;24(11):1106-18 - PubMed
- Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2569-74 - PubMed
- Development. 2011 Sep;138(18):3907-14 - PubMed
- J Biol Chem. 2008 Feb 29;283(9):5496-509 - PubMed
- J Cell Biol. 2012 May 28;197(5):625-41 - PubMed
- Hum Mol Genet. 2012 May 1;21(9):2054-67 - PubMed
- Science. 2011 Apr 22;332(6028):458-61 - PubMed
- Semin Cell Dev Biol. 2012 Sep;23(7):818-26 - PubMed
- Curr Biol. 2009 Apr 28;19(8):675-81 - PubMed
- Nat Cell Biol. 2006 Nov;8(11):1291-7 - PubMed
- Curr Biol. 2008 Dec 9;18(23):1889-95 - PubMed
- Curr Biol. 2009 Nov 3;19(20):1692-702 - PubMed
- Nature. 2011 Jun 08;474(7350):179-83 - PubMed
- Mol Cell Biol. 2005 Sep;25(18):8259-72 - PubMed
- Nat Commun. 2013;4:1877 - PubMed
- J Biol Chem. 2011 Mar 11;286(10):7788-7796 - PubMed
- Semin Cell Dev Biol. 2012 Sep;23(7):794-802 - PubMed
- J Biol Chem. 2008 Oct 10;283(41):27534-27546 - PubMed
- Cancer Res. 2010 Nov 1;70(21):8642-50 - PubMed
- Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4870-5 - PubMed
- Nature. 2013 Jan 3;493(7430):106-10 - PubMed
- J Cell Sci. 2012 Jul 1;125(Pt 13):3085-90 - PubMed
- Cancer Res. 2009 Aug 1;69(15):6033-41 - PubMed
- Trends Cell Biol. 2012 Feb;22(2):88-96 - PubMed
- J Biol Chem. 2011 Feb 18;286(7):5558-66 - PubMed
- Curr Biol. 2008 Mar 11;18(5):311-21 - PubMed
- Curr Biol. 2010 Mar 9;20(5):416-22 - PubMed
- Cell Cycle. 2011 Jun 15;10(12):1897-904 - PubMed
- Neuron. 2012 Mar 22;73(6):1127-42 - PubMed
- Oncogene. 2013 Apr 4;32(14):1821-30 - PubMed
- Cell. 2007 Sep 21;130(6):1120-33 - PubMed
- Genes Dev. 2010 Jan 1;24(1):72-85 - PubMed
- Cell Signal. 2008 Jul;20(7):1237-47 - PubMed
- Cancer Cell. 2009 Nov 6;16(5):425-38 - PubMed
- Curr Biol. 2012 May 8;22(9):R368-79 - PubMed
- J Biol Chem. 2010 Nov 26;285(48):37159-69 - PubMed
- J Biol Chem. 1999 Nov 26;274(48):33847-50 - PubMed
- Mol Cell Biol. 2011 Apr;31(7):1382-95 - PubMed
- Biochem Biophys Res Commun. 2006 Jun 23;345(1):50-8 - PubMed
- Genes Dev. 2007 Nov 1;21(21):2747-61 - PubMed
- Nat Cell Biol. 2004 Jul;6(7):609-17 - PubMed
- EMBO J. 2000 Dec 15;19(24):6778-91 - PubMed
- Nat Rev Mol Cell Biol. 2012 Sep;13(9):591-600 - PubMed
- Curr Biol. 2010 Apr 13;20(7):657-62 - PubMed
- Cell. 2011 Mar 4;144(5):782-95 - PubMed
- Cell. 2003 Aug 22;114(4):445-56 - PubMed
- EMBO J. 2013 May 29;32(11):1543-55 - PubMed
- Dev Cell. 2011 Nov 15;21(5):896-906 - PubMed
- Cell Res. 2011 Oct;21(10):1513-6 - PubMed
- J Clin Invest. 2010 Apr;120(4):1298-309 - PubMed
- Genes Dev. 2011 Apr 15;25(8):814-30 - PubMed
- Circ Res. 2008 Nov 21;103(11):1309-18 - PubMed
- J Biol Chem. 2010 May 14;285(20):15076-15087 - PubMed
- Chem Biol. 2012 Aug 24;19(8):955-62 - PubMed
- Biochem Soc Trans. 2012 Feb;40(1):124-8 - PubMed
- PLoS One. 2013;8(4):e61027 - PubMed
- Genes Dev. 2013 Jan 15;27(2):157-62 - PubMed
- Semin Cell Dev Biol. 2012 Sep;23(7):785-93 - PubMed
- Dev Biol. 2010 Jan 15;337(2):274-83 - PubMed
- Nat Biotechnol. 2009 Sep;27(9):829-39 - PubMed
- Mol Cell Biol. 2008 Apr;28(7):2426-36 - PubMed
- Genes Dev. 2011 Jan 1;25(1):51-63 - PubMed
- Genes Dev. 2012 Jan 1;26(1):54-68 - PubMed
- Cell. 2005 Aug 12;122(3):421-34 - PubMed
- J Cell Biol. 2011 May 16;193(4):633-42 - PubMed
- Genes Cells. 2004 May;9(5):383-97 - PubMed
- Mol Cell Biol. 2013 May;33(9):1859-68 - PubMed
- Free Radic Biol Med. 2012 Jan 15;52(2):507-15 - PubMed
- J Exp Med. 2012 Apr 9;209(4):741-59 - PubMed
- EMBO J. 2011 May 10;30(12):2325-35 - PubMed
- J Biol Chem. 2010 Jun 4;285(23):17329-37 - PubMed
- J Biochem. 2011 Aug;150(2):133-41 - PubMed
- Genes Dev. 2012 Oct 1;26(19):2138-43 - PubMed
- Genes Dev. 2003 Oct 15;17(20):2514-9 - PubMed
- Cell. 2002 Aug 23;110(4):467-78 - PubMed
- Cell. 2005 Mar 11;120(5):675-85 - PubMed
- Dev Dyn. 2012 Jan;241(1):3-15 - PubMed
- J Biol Chem. 2003 Feb 28;278(9):6710-8 - PubMed
- J Cell Biol. 2000 May 29;149(5):1073-86 - PubMed
- EMBO J. 2008 Apr 23;27(8):1231-42 - PubMed
- Dev Cell. 2013 Mar 11;24(5):459-71 - PubMed
- Mol Cell Biol. 2011 Sep;31(17):3603-15 - PubMed
- Cell. 2003 Aug 22;114(4):457-67 - PubMed
- Nat Commun. 2013;4:1822 - PubMed
- Nature. 2006 Sep 14;443(7108):210-3 - PubMed
- Mol Cell. 2008 Feb 15;29(3):350-61 - PubMed
- Cell Cycle. 2011 Aug 15;10(16):2724-36 - PubMed
- EMBO J. 2010 Jan 20;29(2):376-86 - PubMed
- J Biol Chem. 2004 Oct 29;279(44):45773-81 - PubMed
- Cell Signal. 2011 Sep;23(9):1433-40 - PubMed
- Curr Biol. 2012 Sep 11;22(17):1582-6 - PubMed
- EMBO J. 2009 Dec 16;28(24):3879-92 - PubMed
- Liver Int. 2012 Jan;32(1):38-47 - PubMed
- J Biol Chem. 2011 Mar 4;286(9):7018-26 - PubMed
- Nat Rev Cancer. 2013 Apr;13(4):246-57 - PubMed
- PLoS One. 2011;6(9):e24288 - PubMed
- Mol Biol Cell. 2011 Oct;22(19):3725-33 - PubMed
- Oncogene. 2014 Mar 6;33(10):1218-28 - PubMed
- Mol Cell. 2011 Dec 23;44(6):893-906 - PubMed
- Nat Cell Biol. 2013 Jan;15(1):61-71 - PubMed
- Cell Cycle. 2012 Dec 1;11(23):4352-65 - PubMed
- Oncogene. 2008 Mar 20;27(13):1930-8 - PubMed
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