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Updated: Aug 3, 2025
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Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
Published on: December 14, 2017
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PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability
Natalia Martínez1, Teresa Gragera1,2, María Pilar de Lucas1
1Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC) and CIBERONC, Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain.
Oncogenesis
|April 12, 2023
Summary
Protein kinase D (PKD) and the COP9/Signalosome regulate Spry2 protein stability. This interaction impacts Spry2 levels in cancer, suggesting a potential therapeutic target for tumors with reduced Spry2 expression.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- Spry2 modulates tyrosine kinase receptor signaling with cancer-type-specific effects.
- Spry2 protein levels are altered in various cancers and influenced by proteasomal degradation.
Purpose of the Study:
- To investigate the role of protein kinase D (PKD) and the COP9/Signalosome in controlling Spry2 intracellular stability.
Main Methods:
- In vitro and in vivo assays were used to study Spry2 phosphorylation and degradation.
- Experiments involved missense mutation of Spry2 at Serine 112, knockdown of PKD isoforms, and inhibition of PKD kinase activity.
- The effect of CSN3 downregulation on Spry2 stability was assessed.
Main Results:
- PKD phosphorylates Spry2 at Serine 112 and interacts with its C-terminal half.
- Mutation of Ser112 to alanine reduced Spry2 degradation rate.
- PKD inhibition or knockdown, and CSN3 downregulation, led to Spry2 stabilization.
Conclusions:
- PKD and the COP9/Signalosome are key regulators of Spry2 intracellular stability.
- The PKD/COP9 complex represents a potential therapeutic target in cancers with diminished Spry2 expression.
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