title: The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway.
abstract: The Salvador-Warts-Hippo (SWH) pathway is a complex signaling network that controls both developmental and regenerative tissue growth. Using a genetic screen in Drosophila melanogaster, we identified the sterile 20-like kinase, Tao-1, as an SWH pathway member. Tao-1 controls various biological phenomena, including microtubule dynamics, animal behavior, and brain development. Here we describe a role for Tao-1 as a regulator of epithelial tissue growth that modulates activity of the core SWH pathway kinase cassette. Tao-1 functions together with Hippo to activate Warts-mediated repression of Yorkie. Tao-1's ability to control SWH pathway activity is evolutionarily conserved because human TAO1 can suppress activity of the Yorkie ortholog, YAP. Human TAO1 controls SWH pathway activity by phosphorylating, and activating, the Hippo ortholog, MST2. Given that SWH pathway activity is subverted in many human cancers, our findings identify human TAO kinases as potential tumor suppressor genes.
authors.affiliation: Cell Growth and Proliferation Laboratory, Peter MacCallum Cancer Centre, 7 St. Andrews Place, East Melbourne, Victoria 3002, Australia.
authors.forename: Carole L C
authors.initials: CL
authors.lastname: Poon
authors.forename: Jane I
authors.initials: JI
authors.lastname: Lin
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Kieran F
authors.initials: KF
authors.lastname: Harvey
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D004848:Epithelium / Q000254:growth & development* / Q000378:metabolism; D005123:Eye / Q000254:growth & development; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C456659:YY1AP1 protein, human; C503814:Yki protein, Drosophila; C465504:sav protein, Drosophila; C093503:wts protein, Drosophila; C097835:STK3 protein, human; D000099317:Hippo Kinases; C115483:TAO1 protein kinase; C499474:hpo protein, Drosophila