title: The Hippo pathway regulates Wnt/beta-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.
authors.affiliation: Center for Systems Biology, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Xaralabos
authors.initials: X
authors.lastname: Varelas
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Miller
authors.forename: Richelle
authors.initials: R
authors.lastname: Sopko
authors.forename: Siyuan
authors.initials: S
authors.lastname: Song
authors.forename: Alex
authors.initials: A
authors.lastname: Gregorieff
authors.forename: Frederic A
authors.initials: FA
authors.lastname: Fellouse
authors.forename: Rui
authors.initials: R
authors.lastname: Sakuma
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: Walter
authors.initials: W
authors.lastname: Hunziker
authors.forename: Helen
authors.initials: H
authors.lastname: McNeill
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Wrana
authors.forename: Liliana
authors.initials: L
authors.lastname: Attisano
mesh_terms: D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051155:Wnt1 Protein / Q000378:metabolism; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D051153:Wnt Proteins; D051155:Wnt1 Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; C555510:WNT3A protein, human; C555511:Wnt3a protein, mouse; C074622:wg protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases