PUBLICATION
Wnt ligand–dependent activation of the negative feedback regulator Nkd1
- Authors
- Larraguibel, J., Weiss, A.R., Pasula, D.J., Dhaliwal, R.S., Kondra, R., Van Raay, T.J.
- ID
- ZDB-PUB-150424-3
- Date
- 2015
- Source
- Molecular biology of the cell 26(12): 2375-84 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Blastula/metabolism*
- Carrier Proteins/genetics
- Carrier Proteins/metabolism*
- Feedback, Physiological
- Gene Expression Regulation, Developmental
- Membrane Proteins/metabolism
- Signal Transduction
- Wnt Proteins/metabolism*
- Zebrafish/embryology
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- beta Catenin/metabolism
- PubMed
- 25904337 Full text @ Mol. Biol. Cell
Citation
Larraguibel, J., Weiss, A.R., Pasula, D.J., Dhaliwal, R.S., Kondra, R., Van Raay, T.J. (2015) Wnt ligand–dependent activation of the negative feedback regulator Nkd1. Molecular biology of the cell. 26(12):2375-84.
Abstract
Misregulation of Wnt signaling is at the root of many diseases, most notably colorectal cancer and while we understand the activation of the pathway, we have a very poor understanding of the circumstances under which Wnt signaling turns itself off. There are numerous negative feedback regulators of Wnt signaling but two stand out as constitutive and obligate Wnt induced regulators: Axin2 and Nkd1. While Axin2 behaves similar to Axin in the destruction complex, Nkd1 is more enigmatic. Here we use zebrafish blastula cells that are responsive Wnt signaling to demonstrate that Nkd1 activity is specifically dependent on Wnt ligand activation of the receptor. Furthermore, our results support the hypothesis that Nkd1 is recruited to the Wnt signalosome with Dvl2 where it becomes activated to move into the cytoplasm to interact with β-catenin inhibiting its nuclear accumulation. Comparison of these results with Nkd function in Drosophila generates a unified and conserved model on the role of this negative feedback regulator in the modulation of Wnt signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping