Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation

Dev Cell. 2002 Apr;2(4):449-61. doi: 10.1016/s1534-5807(02)00140-5.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Axin Protein
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Casein Kinases
  • Conserved Sequence
  • Cytoskeletal Proteins / antagonists & inhibitors
  • Cytoskeletal Proteins / metabolism*
  • Dishevelled Proteins
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Glycogen Synthase Kinase 3
  • HeLa Cells
  • Humans
  • Hydrogen Bonding
  • In Vitro Techniques
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Molecular Sequence Data
  • Notochord / embryology*
  • Notochord / metabolism
  • Nuclear Proteins*
  • Phenotype
  • Phosphoproteins / metabolism*
  • Protein Binding / physiology
  • Protein Kinases / metabolism
  • Protein Structure, Tertiary
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Repressor Proteins*
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Vertebrates
  • Wnt Proteins
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / genetics*
  • Xenopus Proteins / metabolism*
  • Xenopus laevis
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • Adaptor Proteins, Signal Transducing
  • Axin Protein
  • CTNNB1 protein, Xenopus
  • CTNNB1 protein, human
  • Carrier Proteins
  • Cytoskeletal Proteins
  • DACT1 protein, Xenopus
  • DACT1 protein, human
  • Dact2 protein, mouse
  • Dishevelled Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Trans-Activators
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • axin1 protein, Xenopus
  • beta Catenin
  • Protein Kinases
  • Casein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Glycogen Synthase Kinase 3
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases

Associated data

  • GENBANK/AF488775
  • GENBANK/AF488776
  • GENBANK/BK000256
  • PDB/1LJO