title: Homeodomain-interacting protein kinase regulates Hippo pathway-dependent tissue growth.
abstract: The Salvador-Warts-Hippo (SWH) pathway is an evolutionarily conserved regulator of tissue growth that is deregulated in human cancer. Upstream SWH pathway components convey signals from neighboring cells via a core kinase cassette to the transcription coactivator Yorkie (Yki). Yki controls tissue growth by modulating activity of transcription factors including Scalloped (Sd). To date, five SWH pathway kinases have been identified, but large-scale phosphoproteome studies suggest that unidentified SWH pathway kinases exist. To identify such kinases, we performed an RNA interference screen and isolated homeodomain-interacting protein kinase (Hipk). Unlike previously identified SWH pathway kinases, Hipk is unique in its ability to promote, rather than repress, Yki activity and does so in parallel to the Yki-repressive kinase, Warts (Wts). Hipk is required for basal Yki activity and is likely to regulate Yki function by promoting its accumulation in the nucleus. Like many SWH pathway proteins, Hipk's function is evolutionarily conserved as its closest human homolog, HIPK2, promotes activity of the Yki ortholog YAP in a kinase-dependent fashion. Further, HIPK2 promotes YAP abundance, suggesting that the mechanism by which HIPK2 regulates YAP has diverged in mammals.
authors: Cell Growth and Proliferation Laboratory, Peter MacCallum Cancer Centre, 7 St Andrews Place, East Melbourne, Victoria 3002, Australia.
authors: Carole L C
authors: CL
authors: Poon
authors: Xiaomeng
authors: X
authors: Zhang
authors: Jane I
authors: JI
authors: Lin
authors: Samuel A
authors: SA
authors: Manning
authors: Kieran F
authors: KF
authors: Harvey
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C501861:HIPK protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases