The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index.
Signaling dynamics of the KSR1 scaffold complex
Open accessAbstract
Scaffold proteins contribute to the spatiotemporal control of MAPK signaling and KSR1 is an ERK cascade scaffold that localizes to the plasma membrane in response to growth factor treatment. To better understand the molecular mechanisms of KSR1 function, we examined the interaction of KSR1 with each of the ERK cascade components, Raf, MEK, and ERK. Here, we identify a hydrophobic motif within the proline-rich sequence (PRS) of MEK1 and MEK2 that is required for constitutive binding to KSR1 and find that MEK binding and residues in the KSR1 CA1 region enable KSR1 to form a ternary complex with B-Raf and MEK following growth factor treatment that enhances MEK activation. We also find that docking of active ERK to the KSR1 scaffold allows ERK to phosphorylate KSR1 and B-Raf on feedback S/TP sites. Strikingly, feedback phosphorylation of KSR1 and B-Raf promote their dissociation and result in the release of KSR1 from the plasma membrane. Together, these findings provide unique insight into the signaling dynamics of the KSR1 scaffold and reveal that through regulated interactions with Raf and ERK, KSR1 acts to both potentiate and attenuate ERK cascade activation, thus regulating the intensity and duration of ERK cascade signaling emanating from the plasma membrane during growth factor signaling.
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“Recently, MAPK scaffolds (e.g., KSR) have also been shown to play a key role in modulating the strength and duration of MAPK activation.”
From Molecular basis of MAP kinase regulation (2013) · cites this paper as [13]
Citations
Cites
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Regulation of MAP Kinase Signaling Modules by Scaffold Proteins in Mammals
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Self-citationIntegrating signals from RTKs to ERK/MAPK
Mckay, M., & Morrison, D. K. (2007) · Oncogene · doi:10.1038/sj.onc.1210394 · Cited by 650
Self-citationMP1: A MEK Binding Partner That Enhances Enzymatic Activation of the MAP Kinase Cascade
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Using Engineered Scaffold Interactions to Reshape MAP Kinase Pathway Signaling Dynamics
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KSR, a novel protein kinase required for RAS signal transduction
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Regulation of RAF protein kinases in ERK signalling
Lavoie, H., & Therrien, M. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3979 · Cited by 702
Negative feedback regulation of the ERK1/2 MAPK pathway
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JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships
Zeke, A., Misheva, M., Reményi, A., & Bogoyevitch, M. A. (2016) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00043-14 · Cited by 552
Raf Family Kinases: Old Dogs Have Learned New Tricks
Matallanas, D., Birtwistle, M. R., Romano, D., Zebisch, A., Rauch, J., von Kriegsheim, A., & Kölch, W. (2011) · Genes & Cancer · doi:10.1177/1947601911407323 · Cited by 401
Metadata
- Authors
- McKay, M. M., Ritt, D. A., & Morrison, D. K.
- Affiliations
- Frederick National Laboratory for Cancer Research (US)
- Yale University (US)
- Corresponding author
- Morrison, Deborah K.
- ORCID
- Morrison, Deborah K.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-07-07
- Volume
- 106
- Issue
- 27
- Pages
- 11022-11027
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2708738
- OpenAlex
- W1979514203
- Cited by
- 163
- References
- 35
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 11 · 2021: 12 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 9 · 2016: 14 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 23
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (ZIABC011107)
- 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
- KSR1, scaffold proteins, MAPK signaling, MEK1, MEK2, BRAF, MAPK/ERK pathway, proline-rich sequences, hydrophobic motif, ternary complex, plasma membrane localization, growth factor signaling
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Enzyme Activation, Humans, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Kinases, Signal Transduction, Amino Acid Motifs, Mitogen-Activated Protein Kinase Kinases, Feedback, Physiological, Multiprotein Complexes, Extracellular Signal-Regulated MAP Kinases, Proto-Oncogene Proteins B-raf, Mice, Proline-Rich Protein Domains
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