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Current Biology
Article . 2012
License: Elsevier Non-Commercial
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Article . 2012 . Peer-reviewed
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Homeodomain-Interacting Protein Kinase Regulates Hippo Pathway-Dependent Tissue Growth

Authors: Poon, Carole L.C.; Zhang, Xiaomeng; Lin, Jane I.; Manning, Samuel A.; Harvey, Kieran F.;

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.

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Keywords

Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Apoptosis, YAP-Signaling Proteins, Protein Serine-Threonine Kinases, Gene Expression Regulation, Trans-Activators, Animals, Drosophila Proteins, Wings, Animal, Drosophila, RNA, Messenger, Protein Kinases, Cell Proliferation

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    popularity
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    influence
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
67
Top 10%
Top 10%
Top 10%
hybrid
Related to Research communities
Cancer Research