Abstract
Dapper was isolated in a screen for proteins interacting with Dishevelled, a key factor in Wnt signaling. Dapper and Dishevelled colocalize intracellularly and form a complex with Axin, GSK-3, CKI, and beta-catenin. Overexpression of Dapper increases Axin and GSK-3 in this complex, resulting in decreased soluble beta-catenin and decreased activation of beta-catenin-responsive genes. Dapper also inhibits activation by Dishevelled of c-Jun N-terminal kinase (JNK), a component of beta-catenin-independent Frizzled signaling. Inhibition of Dapper activates both beta-catenin-responsive genes and an AP1-responsive promoter, demonstrating that Dapper is a general Dishevelled antagonist. Depletion of maternal Dapper RNA from Xenopus embryos results in loss of notochord and head structures, demonstrating that Dapper is required for normal vertebrate development.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Axin Protein
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Casein Kinases
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Conserved Sequence
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Cytoskeletal Proteins / antagonists & inhibitors
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Cytoskeletal Proteins / metabolism*
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Dishevelled Proteins
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Gene Deletion
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Gene Expression Regulation, Developmental
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Glycogen Synthase Kinase 3
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HeLa Cells
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Humans
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Hydrogen Bonding
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In Vitro Techniques
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JNK Mitogen-Activated Protein Kinases*
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases / metabolism*
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Molecular Sequence Data
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Notochord / embryology*
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Notochord / metabolism
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Nuclear Proteins*
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Phenotype
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Phosphoproteins / metabolism*
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Protein Binding / physiology
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Protein Kinases / metabolism
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Protein Structure, Tertiary
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Proteins / metabolism
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Proto-Oncogene Proteins / metabolism
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Repressor Proteins*
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Sequence Homology, Amino Acid
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Trans-Activators*
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Vertebrates
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Wnt Proteins
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Xenopus Proteins / chemistry
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Xenopus Proteins / genetics*
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Xenopus Proteins / metabolism*
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Xenopus laevis
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Zebrafish Proteins*
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beta Catenin
Substances
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Adaptor Proteins, Signal Transducing
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Axin Protein
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CTNNB1 protein, Xenopus
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CTNNB1 protein, human
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Carrier Proteins
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Cytoskeletal Proteins
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DACT1 protein, Xenopus
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DACT1 protein, human
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Dact2 protein, mouse
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Dishevelled Proteins
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Nuclear Proteins
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Trans-Activators
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Wnt Proteins
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Xenopus Proteins
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Zebrafish Proteins
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axin1 protein, Xenopus
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beta Catenin
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Protein Kinases
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Casein Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Glycogen Synthase Kinase 3
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases
Associated data
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GENBANK/AF488775
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GENBANK/AF488776
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GENBANK/BK000256
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PDB/1LJO