Document Detail

The FERM-domain protein Expanded regulates Hippo pathway activity via direct interactions with the transcriptional activator Yorkie.
MedLine Citation:
PMID:  19289086     Owner:  NLM     Status:  MEDLINE    
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.
Caroline Badouel; Laura Gardano; Nancy Amin; Ankush Garg; Robyn Rosenfeld; Thierry Le Bihan; Helen McNeill
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Developmental cell     Volume:  16     ISSN:  1878-1551     ISO Abbreviation:  Dev. Cell     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-17     Completed Date:  2009-04-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  411-20     Citation Subset:  IM    
Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada.
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MeSH Terms
Amino Acid Motifs
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*
Grant Support
//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
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 Kinases; EC protein, Drosophila
Comment In:
Dev Cell. 2009 Mar;16(3):321-2   [PMID:  19289076 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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