Project information
Odhalení tajemství signální dráhy WNT analýzou struktury proteinu Dishevelled
- Project Identification
- GA18-17658S
- Project Period
- 1/2018 - 12/2020
- Investor / Pogramme / Project type
-
Czech Science Foundation
- Standard Projects
- MU Faculty or unit
- Faculty of Science
The proposal aims is to describe dynamics of DVL conformation and understand mechanisms that control it. We will take advantage of recent advances in structural proteomics/structural biology and unique reagents/unpublished information gathered in the PI’s laboratory (i) to describe DVL conformations and monitor their dynamics using combination of FRET and methods of structural proteomics, and (ii) to produce DVL protein/DVL-based complexes in the amount that would allow us, as an ultimate goal, to perform structural analysis of individual DVL-based molecular machineries. This project will open the way towards the structural biology of physiological DVL complexes, which will allow the design of new drugs that will interfere with the individual DVL functions in order to inhibit overactive Wnt signaling or bypass Wnt loss-of-function in pathological conditions.
Publications
Total number of publications: 7
2021
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Phosphorylation-induced changes in the PDZ domain of Dishevelled 3
Scientific Reports, year: 2021, volume: 11, edition: 1, DOI
2020
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Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling
EMBO MOLECULAR MEDICINE, year: 2020, volume: 12, edition: 11, DOI
2019
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Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs
Cell Communication and Signaling, year: 2019, volume: 17, edition: 1, DOI
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Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1
Nature Communications, year: 2019, volume: 10, edition: APR 18 2019, DOI
2018
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Analysis of binding interfaces of the human scaffold protein AXIN1 by peptide microarrays
Journal of Biological Chemistry, year: 2018, volume: 293, edition: 42, DOI
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Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner
Nature Communications, year: 2018, volume: 9, edition: 1, DOI
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The planar cell polarity protein VANG-1/Vangl negatively regulates Wnt/beta-catenin signaling through a Dvl dependent mechanism
PLoS Genetics, year: 2018, volume: 14, edition: 12, DOI