The Sterile 20-like Kinase Tao-1 Controls Tissue Growth by Regulating the Salvador-Warts-Hippo Pathway

• Published in: Developmental cell 2011-11, Vol.21 (5), p.896-906
• Main Authors: Poon, Carole L.C., Lin, Jane I., Zhang, Xiaomeng, Harvey, Kieran F.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Cycle Proteins - metabolism; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell physiology; Conserved Sequence; Drosophila melanogaster - enzymology; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Epithelium - growth & development; Epithelium - metabolism; Eye - growth & development; Female; Fundamental and applied biological sciences. Psychology; Human viral diseases; Humans; Infectious diseases; Intracellular Signaling Peptides and Proteins - metabolism; MAP Kinase Kinase Kinases - metabolism; Medical sciences; Molecular and cellular biology; Nuclear Proteins - metabolism; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction; Trans-Activators - metabolism; Transcription Factors - metabolism; Viral diseases; Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye; Wings, Animal - growth & development
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2011.09.012

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. [Display omitted] ► Tao-1 kinase regulates the growth of developing epithelial tissues in Drosophila ► Tao-1 regulates SWH pathway activity in both Drosophila and human cultured cells ► Tao-1 functions together with Hippo to activate Warts and suppress Yorkie ► Human TAO1 can phosphorylate and activate human MST2