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KSR is a scaffold required for activation of the ERK/MAPK module
Open accessAbstract
Mechanisms that regulate signal propagation through the ERK/MAPK pathway are still poorly understood. Several proteins are suspected to play critical roles in this process. One of these is Kinase Suppressor of Ras (KSR), a component previously identified in RAS-dependent genetic screens in Drosophila and Caenorhabditis elegans . Here, we show that KSR functions upstream of MEK within the ERK/MAPK module. In agreement with this, we found that KSR facilitates the phosphorylation of MEK by RAF. We further show that KSR associates independently with RAF and MEK, and that these interactions lead to the formation of a RAF/MEK complex, thereby positioning RAF in close proximity to its substrate MEK. These findings suggest that KSR functions as a scaffold that assembles the RAF/MEK functional pair.
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“both of which promote ERK signaling (133–136)”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [134]
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Metadata
- Authors
- Roy, F., Laberge, G., Douziech, M., Ferland-McCollough, D., & Therrien, M.
- Affiliations
- Montreal Clinical Research Institute (CA)
- Corresponding author
- Therrien, Marc
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-02-15
- Volume
- 16
- Issue
- 4
- Pages
- 427-438
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC155344
- OpenAlex
- W2099267053
- Cited by
- 217
- References
- 40
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 9 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 7 · 2013: 9 · 2012: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- KSR, MAPK/ERK pathway, MEK phosphorylation, Raf, scaffold proteins, signal transduction, Ras signaling, protein-protein interaction
- MeSH terms
- Animals, Cells, Cultured, Drosophila melanogaster, Phosphorylation, Protein Kinases, Protein Processing, Post-Translational, Recombinant Fusion Proteins, Transfection, ras Proteins, Proto-Oncogene Proteins c-raf, Mitogen-Activated Protein Kinase Kinases, MAP Kinase Signaling System, Drosophila Proteins, Macromolecular Substances
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