Journal
DEVELOPMENTAL CELL
Volume 2, Issue 4, Pages 449-461Publisher
CELL PRESS
DOI: 10.1016/S1534-5807(02)00140-5
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Funding
- NICHD NIH HHS [R01 HD27525, T32 HD007183, 2T32 HD07183-21] Funding Source: Medline
- NIMH NIH HHS [K08 MH01750] Funding Source: Medline
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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.
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