| The FERM-domain protein Expanded regulates Hippo pathway activity via direct interactions with the transcriptional activator Yorkie. | |
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MedLine Citation:
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PMID: 19289086 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The Hippo kinase pathway plays a central role in growth regulation and tumor suppression from flies to man. The Hippo/Mst kinase phosphorylates and activates the NDR family kinase Warts/Lats, which phosphorylates and inhibits the transcriptional activator Yorkie/YAP. Current models place the FERM-domain protein Expanded upstream of Hippo kinase in growth control. To understand how Expanded regulates Hippo pathway activity, we used affinity chromatography and mass spectrometry to identify Expanded-binding proteins. Surprisingly we find that Yorkie is the major Expanded-binding protein in Drosophila S2 cells. Expanded binds Yorkie at endogenous levels via WW-domain-PPxY interactions, independently of Yorkie phosphorylation at S168, which is critical for 14-3-3 binding. Expanded relocalizes Yorkie from the nucleus, abrogating its nuclear activity, and it can regulate growth downstream of warts in vivo. These data lead to a new model whereby Expanded functions downstream of Warts, in concert with 14-3-3 proteins to sequester Yorkie in the cytoplasm, inhibiting growth activity of the Hippo pathway. |
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Authors:
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Caroline Badouel; Laura Gardano; Nancy Amin; Ankush Garg; Robyn Rosenfeld; Thierry Le Bihan; Helen McNeill |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Developmental cell Volume: 16 ISSN: 1878-1551 ISO Abbreviation: Dev. Cell Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-03-17 Completed Date: 2009-04-02 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101120028 Medline TA: Dev Cell Country: United States |
Other Details:
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Languages: eng Pagination: 411-20 Citation Subset: IM |
Affiliation:
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Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Motifs Animals Animals, Genetically Modified Cell Line Cytoplasm / metabolism Drosophila / genetics, metabolism Drosophila Proteins / chemistry, genetics, metabolism* Intracellular Signaling Peptides and Proteins / genetics, metabolism* Membrane Proteins / chemistry, genetics, metabolism* Models, Biological Nuclear Proteins / genetics, metabolism* Protein Binding Protein Kinases / genetics, metabolism Protein Structure, Tertiary Protein-Serine-Threonine Kinases / genetics, metabolism* Recombinant Proteins / chemistry, genetics, metabolism Sequence Deletion Signal Transduction Trans-Activators / genetics, metabolism* Transfection |
| Grant Support | |
ID/Acronym/Agency:
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//Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
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0/Drosophila Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Nuclear Proteins; 0/Recombinant Proteins; 0/Trans-Activators; 0/Yorkie protein, Drosophila; 0/expanded protein, Drosophila; EC 2.7.-/Protein Kinases; EC 2.7.1.-/warts protein, Drosophila; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/hpo protein, Drosophila |
| Comments/Corrections | |
Comment In:
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Dev Cell. 2009 Mar;16(3):321-2
[PMID:
19289076
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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