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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

Published on: January 2, 2018

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Ras-activated Dsor1 promotes Wnt signaling in Drosophila development

Eric T Hall1, Esther M Verheyen2

  • 1Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.

Journal of Cell Science
|November 7, 2015
PubMed

Insights

The dual specificity kinase Dsor1 (MAP2K1/2) is essential for Wnt signaling by stabilizing Armadillo (β-catenin). This study reveals a novel crosstalk between insulin and Wnt pathways mediated by Dsor1.

Area of Science:

  • Cellular signaling pathways
  • Developmental biology
  • Cancer research

Background:

  • Wnt/Wingless (Wg) and Ras-MAPK signaling are crucial for cell growth and fate.
  • Dysregulation of these pathways is linked to tumorigenesis.
  • Interactions between Ras-MAPK and Wnt signaling can be synergistic or antagonistic.

Purpose of the Study:

  • To investigate the role of Downstream of Raf1 (Dsor1), a MEK1/2 homolog, in Wnt signaling.
  • To elucidate the mechanism of interaction between Dsor1 and Wnt signaling components.
  • To identify upstream regulators of Dsor1 in this context.

Main Methods:

  • Drosophila melanogaster as a model organism.
  • Gene knockdown techniques to assess Dsor1 function.
  • Analysis of Wnt target gene expression and Armadillo (Arm) protein levels.
  • Co-immunoprecipitation to detect physical interactions.

Main Results:

  • Dsor1 knockdown leads to loss of Wg target gene expression and reduced stabilized Arm.
  • Dsor1 physically interacts with Armadillo.
  • Catalytically inactive Dsor1 impairs active Arm levels, suggesting Dsor1 counteracts Arm destruction.
  • Dsor1 activation is independent of EGFR and appears linked to the insulin-like growth factor receptor.

Conclusions:

  • Dsor1 is a novel and essential component of the Wnt signaling pathway in Drosophila.
  • Dsor1 stabilizes Armadillo, potentially by inhibiting its degradation.
  • A new crosstalk pathway exists between insulin signaling and Wnt signaling, mediated by Dsor1.
Keywords:
Dsor1EGFRInRMAPKMEKWinglessWnt

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