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Updated: Jul 24, 2025
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Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
Published on: November 29, 2016
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RAS-independent ERK activation by constitutively active KSR3 in non-chordate metazoa
Aline Chessel1, Noémie De Crozé1, Maria Dolores Molina2
1Institut de Biologie Valrose CNRS, Université Côte d'Azur, Nice, France.
Nature Communications
|July 5, 2023
Summary
Researchers discovered a new mechanism for ERK signaling activation in sea urchin embryos involving a novel protein, KSR3. This finding sheds light on the evolution of signaling pathways and has implications for understanding human cancer mutations.
Area of Science:
- Developmental Biology
- Molecular Biology
- Evolutionary Biology
Background:
- ERK signaling is crucial for cell development but its activation mechanism in sea urchin mesodermal precursors was unknown.
- Existing knowledge suggested extracellular ligands triggered ERK, but this was not observed in early sea urchin development.
Purpose of the Study:
- To elucidate the cell-autonomous, RAS-independent mechanism of ERK signaling activation in sea urchin mesodermal precursors.
- To identify novel proteins involved in regulating ERK signaling during early embryonic development.
Main Methods:
- Transcriptional analysis to identify genes involved in ERK activation.
- Phylogenetic analysis to trace the evolutionary history of identified genes.
- Functional assays in cultured cells to test the activity of the identified protein.
Main Results:
- Discovered KSR3, a protein activating ERK signaling transcriptionally, independent of RAS.
- KSR3 belongs to a family of catalytically inactive RAF activators found in many invertebrates but lost in flies and nematodes.
- KSR3 structure resembles oncogenic human RAF mutants, and KSR3 activates ERK signaling independently of RAS in cultured cells.
Conclusions:
- KSR3 family proteins are key activators of RAS-independent ERK signaling in invertebrates.
- Findings provide insights into the evolution of the ERK pathway and suggest mechanisms for its evolutionary co-option.
- Identified KSR3 sequences to discover activating mutations in human B-RAF, linking invertebrate mechanisms to human cancer.
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