Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity.
Publication Year
2003
Type
Journal Article
Abstract
Activation of the Wnt signaling cascade provides key signals during development and in disease. Here we provide evidence, by designing a Wnt receptor with ligand-independent signaling activity, that physical proximity of Arrow (LRP) to the Wnt receptor Frizzled-2 triggers the intracellular signaling cascade. We have uncovered a branch of the Wnt pathway in which Armadillo activity is regulated concomitantly with the levels of Axin protein. The intracellular pathway bypasses Gsk3beta/Zw3, the kinase normally required for controlling beta-catenin/Armadillo levels, suggesting that modulated degradation of Armadillo is not required for Wnt signaling. We propose that Arrow (LRP) recruits Axin to the membrane, and that this interaction leads to Axin degradation. As a consequence, Armadillo is no longer bound by Axin, resulting in nuclear signaling by Armadillo.
Keywords
Animals,
signal transduction,
Mutation,
Transcription Factors,
Trans-Activators,
Membrane Proteins,
Recombinant Fusion Proteins,
Receptors, Cell Surface,
Carrier Proteins,
Female,
Gene Expression Regulation, Developmental,
Embryo, Nonmammalian,
Drosophila melanogaster,
Active Transport, Cell Nucleus,
Adaptor Proteins, Signal Transducing,
Drosophila Proteins,
Proto-Oncogene Proteins,
Glycogen Synthase Kinase 3,
Armadillo Domain Proteins,
Frizzled Receptors,
Glycogen Synthase Kinase 3 beta,
LDL-Receptor Related Proteins,
Low Density Lipoprotein Receptor-Related Protein-5,
Receptors, G-Protein-Coupled,
Receptors, LDL,
Wnt1 Protein
Journal
Dev Cell
Volume
4
Issue
3
Pages
407-18
Date Published
03/2003
ISSN Number
1534-5807
Alternate Journal
Dev. Cell
PMID
12636921