Cited by 217Protein Kinase Regulation and GTPase SignalingMelanoma and MAPK PathwaysProtein Tyrosine Phosphatases

KSR is a scaffold required for activation of the ERK/MAPK module

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Roy, François, Laberge, Gino, Douziech, Mélanie, Ferland-McCollough, David, Therrien, Marc·2002·Genes & Development

Abstract

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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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
Published
2002-02-15
Volume
16
Issue
4
Pages
427-438
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
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
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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