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Developmental Cell
Article
License: Elsevier Non-Commercial
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Developmental Cell
Article . 2010
License: Elsevier Non-Commercial
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Developmental Cell
Article . 2010 . Peer-reviewed
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The Hippo Pathway Regulates Wnt/β-Catenin Signaling

Authors: Varelas, Xaralabos; Miller, Bryan W.; Sopko, Richelle; Song, Siyuan; Gregorieff, Alex; Fellouse, Frederic A.; Sakuma, Rui; +5 Authors

The Hippo Pathway Regulates Wnt/β-Catenin Signaling

Abstract

Several developmental pathways contribute to processes that regulate tissue growth and organ size. The Hippo pathway has emerged as one such critical regulator. However, how Hippo signaling is integrated with other pathways to coordinate these processes remains unclear. Here, we show that the Hippo pathway restricts Wnt/beta-Catenin signaling by promoting an interaction between TAZ and DVL in the cytoplasm. TAZ inhibits the CK1delta/epsilon-mediated phosphorylation of DVL, thereby inhibiting Wnt/beta-Catenin signaling. Abrogation of TAZ levels or Hippo signaling enhances Wnt3A-stimulated DVL phosphorylation, nuclear beta-Catenin, and Wnt target gene expression. Mice lacking Taz develop polycystic kidneys with enhanced cytoplasmic and nuclear beta-Catenin. Moreover, in Drosophila, Hippo signaling modulates Wg target gene expression. These results uncover a cytoplasmic function of TAZ in regulating Wnt signaling and highlight the role of the Hippo pathway in coordinating morphogenetic signaling with growth control.

Keywords

Cytoplasm, Gene Expression Profiling, Intracellular Signaling Peptides and Proteins, Hippo Kinases, Wnt1 Protein, Protein Serine-Threonine Kinases, Models, Biological, Cell Line, Wnt Proteins, Wnt3 Protein, Mice, Gene Expression Regulation, SIGNALING, Wnt3A Protein, Animals, Drosophila Proteins, Humans, CELLBIO, Phosphorylation, beta Catenin, Developmental Biology, Signal Transduction

  • BIP!
    Impact byBIP!
    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).
    545
    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.
    Top 0.1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 1%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 0.1%
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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!
545
Top 0.1%
Top 1%
Top 0.1%
hybrid